10.5826/dpc.1302a85
Introduction: Psoriasis is a chronic inflammatory dermatological disease with complex pathogenesis in which many immune system cells, including keratinocytes, play a role. Many genes regulate the proliferation of keratinocytes and other immune cells that have essential roles in the pathogenesis of psoriasis.The expressions of EREG, PTPN1, and SERPINB7 genes were shown as upregulated in psoriatic skins in a few studies previously.
Objectives: We aimed to evaluate the expressions of these genes in psoriatic lesional skin and com-pared them with non-lesional adjacent skin of the same patients and normal skin of healthy controls.
Results: Our results revealed that the expressions of EREG and PTPN1 genes were upregulated,whereas the SERPINB7 gene expression was down regulated in the psoriatic skin of the patients than normal skin of controls. Moreover, the expression level of the SERPINB7 gene was also negatively correlated with the severity of the disease among patients.
Conclusions: According to our results, overexpression of EREG and PTPN1 genes, and decreased expression of SERPINB7 gene may lead to the development of psoriasis.
text/xml
2160-9381
2650
en
Mehmet  Yıldırım
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
serine proteinase inhibitors
The Role of EREG, PTPN1, and SERPINB7 Genes in the Pathogenesis of Psoriasis: May SERPINB7 Be Protective and a Marker of Severity for Psoriasis? 
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2023-04-29
2022-06-14
2023-04-29
2023-05-31
e2023085
Dermatol Pract Concept
Introduction: Psoriasis is a chronic inflammatory dermatological disease with complex pathogenesis in which many immune system cells, including keratinocytes, play a role. Many genes regulate the proliferation of keratinocytes and other immune cells that have essential roles in the pathogenesis of psoriasis.The expressions of EREG, PTPN1, and SERPINB7 genes were shown as upregulated in psoriatic skins in a few studies previously.
Objectives: We aimed to evaluate the expressions of these genes in psoriatic lesional skin and com-pared them with non-lesional adjacent skin of the same patients and normal skin of healthy controls.
Results: Our results revealed that the expressions of EREG and PTPN1 genes were upregulated,whereas the SERPINB7 gene expression was down regulated in the psoriatic skin of the patients than normal skin of controls. Moreover, the expression level of the SERPINB7 gene was also negatively correlated with the severity of the disease among patients.
Conclusions: According to our results, overexpression of EREG and PTPN1 genes, and decreased expression of SERPINB7 gene may lead to the development of psoriasis.
Mehmet  Yıldırım
2023/04/29
10.5826/dpc.1302a85
e2023085
Department of Dermatology, Faculty of Medicine, Suleyman Demirel University, Isparta/Turkey
2160-9381
serine proteinase inhibitors
en
e2023085
Shiiba M, Nomura H, Shinozuka K, et al. Down-regulated expression of SERPIN genes located on chromosome 18q21 in oral squamous cell carcinomas. Oncol Rep. 2010;24(1):241-249.
The Role of EREG, PTPN1, and SERPINB7 Genes in the Pathogenesis of Psoriasis: May SERPINB7 Be Protective and a Marker of Severity for Psoriasis? 
https://dpcj.org/index.php/dpc/article/download/2650/2057
  The Role of EREG, PTPN1, and SERPINB7 Genes in
   the Pathogenesis of Psoriasis: May SERPINB7 Be
  Protective and a Marker of Severity for Psoriasis?
        Havva Hilal Ayvaz1, Kuyaş Hekimler Öztürk2, Mehmet Ali Seyirci1, Emrah Atay3,
                      Selma Korkmaz1, İjlal Erturan1, Mehmet Yıldırım1


1 Department of Dermatology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey
2 Department of Medical Genetics, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey
3 Public health expertise, Eskişehir Directorate of Health, Eskişehir, Turkey



Key words: psoriasis, epiregulin, tyrosine-protein phosphatase non-receptor type 1, serine proteinase inhibitors
Citation: Ayvaz HH, Öztürk KH, Seyirci MA, et al. The role of EREG, PTPN1, and SERPINB7 genes in the pathogenesis of psoriasis:
May SERPINB7 be protective and a marker of severity for psoriasis? Dermatol Pract Concept. 2023;13(2):e2023085. DOI: https://doi​
.org/10.5826/dpc.1302a85
Accepted: September 26, 2022; Published: April 2023
Copyright: ©2023 Ayvaz et al. This is an open-access article distributed under the terms of the Creative Commons
Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted
noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing Interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding Author: Havva Hilal Ayvaz, Çünür Mah SDÜ Dermatology Department, 32260, Isparta, TURKEY.
E-mail: drhhilalayvaz@gmail.com, Phone number: +905309505907




  ABSTRACT             Introduction: Psoriasis is a chronic inflammatory dermatological disease with complex pathogenesis
                       in which many immune system cells, including keratinocytes, play a role. Many genes regulate the
                       proliferation of keratinocytes and other immune cells that have essential roles in the pathogenesis
                       of psoriasis. The expressions of EREG, PTPN1, and SERPINB7 genes were shown as upregulated in
                       psoriatic skins in a few studies previously.
                       Objectives: We aimed to evaluate the expressions of these genes in psoriatic lesional skin and com-
                       pared them with non-lesional adjacent skin of the same patients and normal skin of healthy controls.
                       Results: Our results revealed that the expressions of EREG and PTPN1 genes were upregulated,
                       whereas the SERPINB7 gene expression was down regulated in the psoriatic skin of the patients than
                       normal skin of controls. Moreover, the expression level of the SERPINB7 gene was also negatively
                       correlated with the severity of the disease among patients.
                       Conclusions: According to our results, overexpression of EREG and PTPN1 genes, and decreased
                       expression of SERPINB7 gene may lead to the development of psoriasis.




Original Article | Dermatol Pract Concept. 2023;13(2):e2023085                                                                      1
Introduction                                                       was taken, skin examination was performed, and the pres-
                                                                   ence of arthritis or nail involvement was also examined and
Psoriasis is an auto-inflammatory dermatological disease           noted by the same physician. Psoriasis area and severity in-
with complex pathogenesis, including immunological, bio-           dex (PASI) scores were calculated, and according to the PASI
chemical, vascular, and neurological changes [1]. The main         scores, patients were divided into two subgroups: a mild dis-
pathological findings of psoriasis are the hyperproliferation      ease with PASI score ≤ 10, moderate-severe disease with PASI
of epidermis, altered keratinocytes, dermal angiogenesis, a        score > 10 [11].
dense epidermal and dermal infiltrate consisting of macro-            All participants were selected from patients not treated
phages, lymphocytes, and neutrophils [2]. Keratinocytes are        with systemic therapy, including phototherapy, for at least
one of the principal cells playing essential roles in the patho-   eight weeks before the study entry. Age- and sex-matched 11
genesis of psoriasis and, many cytokines and chemokines            healthy volunteers without any systemic inflammatory dis-
regulate the proliferation of them. The most important signal      eases, including cardiovascular and/or neurovascular diseases,
for proliferation of keratinocytes comes from the epidermal        inflammatory skin disorders, and regular drug intake for any
growth factor (EGF) receptor, and epiregulin (EREG) is a           reason, were also enrolled as the control group. Patients with
member of the EGF family [3].                                      a history of cardiovascular or cerebrovascular events, active
    Serpin Family B Member 7 (SERPINB7) is a cytoplasmic           infection, and inflammatory systemic (including diabetes mel-
member of the serine protease inhibitor family that can alter      litus [DM]) or skin diseases, other autoimmune diseases, and/
the epithelium of the skin, and also protects keratinocytes        or malignancy in the last 5 years were excluded.
from oxidative stress-mediated cellular damage [4].                   Skin samples, 3 mm in size, were collected from 25 pa-
    Protein Tyrosine Phosphatase Non-Receptor Type 1               tients with psoriasis and 11 healthy controls. The lesional
(PTPN1) is a member of the PTP family that has regulatory          and non‑lesional psoriatic skin (each 3 mm in size) were
effects on Munc18c protein, which interacts with SNARE             taken from each patient with psoriasis and one skin sample
in adipocytes, insulin signaling pathways, and also immuno-        in similar size from healthy controls. These skin tissues were
logical processes which may also be related to its role in the     taken into DNAse RNase-free 1.5 ml Eppendorf tubes and
pathogenesis of psoriasis [5,6].                                   stored in the refrigerator at ‑80˚C.


                                                                   mRNA Extraction and cDNA Synthesis
Objectives
                                                                   mRNA isolation from tissue samples belonging to the study
In the literature, the expression of EREG, PTPN1, and SER-         group was performed with Hybrid-RTM mRNA Isolation
PINB7 genes have been evaluated in a few studies, and these        Kit (GeneAll Biotechnology) according to the manufac-
genes are claimed to be novel susceptible genes for psoriasis      turer instructions. The concentration and purity of isolated
especially related to keratinocytes, adipocytes, other immu-       total mRNAs were measured with a Thermo Fisher Nano-
nological cells [2,7-10]. Unlike these studies, we investigated    DropTM spectrophotometer. WizScript™ cDNA Synthesis
all these genes together, at the tissue level, and in more sam-    Kit (Wizbio) was used to obtain cDNA from the obtained
ples. We also compared the genes expressions between le-           mRNA. Reverse transcription was performed using the Sim-
sional skin and non-lesional adjacent skin of patients with        pliAmp Thermal Cycler (Thermo Fisher Scientific) according
psoriasis, and normal skin of healthy controls.                    to the manufacturer instructions. Obtained cDNA samples
                                                                   were stored at -80ºC until real-time (RT)-PCR analysis.

Methods
                                                                   Primary Sequences and Quantitation of Genes
The present prospective case-control study was performed           The sequence used for EREG (Accession No: NM_001432)
according to the Declaration of Helsinki guidelines and ap-        includes primers as follows. F: GGACAGTGCATCTATCTG-
proved by the Ethics Committee of Suleyman Demirel Med-            GTGG, R: TTGGTGGACGGTTAAAAAGAAGT, for PTPN1
ical Faculty (decision 11 on 16.01.2020). All participants in      (Accession No: NM_002827) F: GCAGATCGACAAGTC-
the study were provided informed consent.                          CGGG, R: GCCACTCTACATGGGAAGTCAC, for SERPINB7
                                                                   (Accession No: NM_001040147) F: TAAGCTCATCTGCTG-
Study Population                                                   TAATGGTG, R: GGCAATTTATGGTTTCGCTCTTG, for
Twenty-five patients diagnosed with psoriasis clinically and       ACTB (Accession No: NM_001101) F: CATGTACGTTGC-
histopathologically, aged over 18 and under 65 years, pre-         TATCCAGGC R: CTCCTTAATGTCACGCACGAT.
senting to the dermatology outpatient clinic of Suleyman              Quantitation of the obtained mRNAs was performed
Demirel Medical Faculty between February 2020 and Janu-            with Rotor-Gene Q (Qiagen, Hiden) according to the manu-
ary 2021, were considered for this study. Detailed anamnesis       facturer instructions. mRNAs were analyzed by SYBR green


2                                                                      Original Article | Dermatol Pract Concept. 2023;13(2):e2023085
method using β-Actin (ACTB as an internal control, house-               10 (40%) had psoriatic arthritis, and 14 (56%) had a posi-
keeping gene). Cycle threshold (CT) values of mRNAs were                tive family history. Patients and controls had approximately
determined, and the obtained CT values were normalized to               similar body mass index (26.06 kg/m2 versus 26.76 kg/m2)
ACTB. The fold change of each mRNA expression was cal-                  (P = 0.946). Descriptive features of the participants were
culated using the 2−ΔΔCt equation.                                      given in Table 1.


Statistical Analysis                                                    Gene Expression Levels in Tissue Samples
Data were analyzed using IBM SPSS Statistics 27.0. The de-              In the real time (RT)-PCR analysis, we observed that the
scriptive values of participants were presented as mean ±               EREG gene expression level was significantly upregu-
standard deviation (SD) (also minimum and maximum val-                  lated in the lesional psoriatic skin tissue compared to the
ues). The categorical variables were presented as frequency             non-lesional psoriatic tissue (FC=1.60, P = 0.010). In ad-
and percentage. Chi-Square analysis was used for categorical            dition, a significant down-regulation was demonstrated
variables. The distribution characteristics were first exam-            in the expression levels of the EREG gene in the adjacent
ined with the Shapiro Wilk test to analyze continuous vari-             non-lesional skin tissue of patients compared to the healthy
ables across groups. Mann Whitney U or Kruskal Wallis test              skin tissue of controls (FC = -1.82, P = 0.001) (Table 2). It
was used for non-parametric distributions according to the              was observed that PTPN1 gene expression level was signifi-
number of groups. For analysis of 2 scale/continuous type               cantly increased in the lesional tissue compared to healthy
variables, Spearman correlation analysis was used. P value <            control tissue (FC = 2.44, P < 0.001). In addition, no differ-
0.05 was accepted as statistically significant for all analyses.        ence was found in the expression levels of the PTPN1 gene
                                                                        in the adjacent non-lesional skin tissue of psoriasis patients

Results                                                                 compared to the healthy skin tissue of controls (FC = -1.35,
                                                                        P > 0.05) (Table 2). It was observed that the expression
Twenty-five patients (13 females and 12 males) with a mean              level of the SERPINB7 gene was significantly decreased
age of 39.8 ± 13.72 years and 11 control (6 females and                 in psoriatic tissue compared to the healthy control tissue
5 males) subjects with a mean age of 40.6 ± 14.07 years were            (FC = -2.33, P < 0.001). Moreover, no significant difference
included in the study. No significant difference was found              was seen in the expression levels of the SERPINB7 gene in
between the groups regarding mean age and sex (P = 0.866,               the adjacent non-lesional skin tissue of psoriasis patients
P = 0.999 respectively). The mean duration of the disease in            compared to the healthy skin tissue of controls (FC = -9.1,
the patient group was 9.8 years, and the mean PASI score was            P > 0.05) (Table 2). According to these results, the expres-
13.3 ± 6.1. According to the PASI scores, 12 (48%) patients             sion levels of all genes were significantly different between
had mild, and 13 (52%) patients had moderate-severe psori-              psoriatic skin and healthy control skin (for all P < 0.05)
asis. Furthermore, 13 patients (52%) had nail involvement,              (Figure 1).



                                 Table 1. Baseline characteristics of the study groups.
                                                   Patient group (N = 25) Control group (N = 11)                       Pa
 Age, years, mean ± SD                                   39.8 ± 13.72                 40.6 ± 14.07                   .866
 Sex
    Female, N (%)                                          13 (52%)                    6 (45.5%)                     .999
    Male, N (%)                                            12 (48%)                    5 (54.5%)
 BMI, mean ± SD                                           26.06 ± 4.8                 26.19± 3.18                    .946
 Duration of disease, years, mean ± SD                 9.8 ± 9.2 (1-35)b                    -
 PASI scores, mean ± SD                                   13.3 ± 6.1                        -
 Arthritis, N (%)                                          10 (40%)                         -
 Nail involvement, N (%)                                   13 (52%)                         -
 Positive family history, N (%)                            14 (56%)                         -
 Severity of the disease
    Mild disease, N (%)                                    12 (48%)                         -
    Moderate-severe disease, N (%)                         13 (52%)

BMI = body mass index; PASI = psoriasis area and severity index; SD = standard deviation.
a
  P value is significant at the 0.05 level
b
  Minimum and maximum values



Original Article | Dermatol Pract Concept. 2023;13(2):e2023085                                                                      3
Table 2. Comparison of the expression of EREG, PTPN1, and SERPINB7 genes between the lesional
        and non-lesional skins of the psoriatic patients and normal skins of healthy controls.
                                                       Lesional skin of    Non-lesional skin of
                                                      psoriatic patients    psoriatic patients       Controls          Pa             Pb
                                                                                                                               AB:<0.001
                                                         1.82 ± 0.95            0.57 ± 0.2          1.03 ± 0.3
 EREG, mean ± SD (min-max)                                                                                          0.012      AC:0.345
                                                          (0.6-4.11)           (0.34-1.06)          (0.7-1.68)
                                                                                                                                BC:0.004
                                                                                                                               AB:<0.001
                                                         3.76 ± 1.89           1.18 ± 0.57            1 ± 0.13
 PTPN1, mean ± SD (min-max)                                                                                        <0.001      AC:<0.001
                                                         (1.26-10.6)           (0.24-2.19)          (0.86-1.24)
                                                                                                                                BC:0.999
                                                                                                                               AB:<0.001
                                                         2.54 ± 0.61           4.49 ± 0.42          4.29 ± 0.32
 SERPINB7, mean ± SD (min-max)                                                                                  <0.001         AC:<0.001
                                                          (1.5-4.14)           (3.95-5.31)          (3.79-4.72)
                                                                                                                                BC:0.999

A = lesional skin of patients; B = non-lesional skin of patients; C = normal skin of controls; EREG = epiregulin; PTPN1 = tyrosine-protein
phosphatase non-receptor type 1; SD = standard deviation; SERPINB7 = serpin family B member 7.
a
  triple comparison of the groups (with Kruskal-Wallis, P < 0.05 is accepted as statistically significant)
b
  pairwise comparison of the groups (Bonferroni correction was used, and P < 0.05 is accepted as statistically significant)



                              5,00

                              4,50

                              4,00

                              3,50
           MRNA FOLD CHANGE




                              3,00

                              2,50

                              2,00

                              1,50

                              1,00

                              0,50

                              0,00
                                             EREG                           PTPN1                           SERPINB7
                              -0,50




                                      LESIONAL SKIN           NON-LESIONAL ADJACENT SKIN                NORMAL SKIN


           Figure 1. Comparison of the expression levels of EREG, PTPN1, SERPINB7 genes between the lesional and non-­
           lesional skins of the psoriatic patients and the normal skin of healthy controls. RT-PCR analysis of the indicated genes
           in indicated skin tissues was performed.
           * P < 0.05; ** P < 0.001
           EREG = epiregulin; PTPN1 = tyrosine-protein phosphatase non-receptor type 1; SERPINB7 = serpin family B member 7.



    Furthermore, the decrease of the expression of the
                                                                            Conclusions
SERPINB7 gene was correlated with PASI scores in the pa-
tient group (P = 0.038, r = 0.417) (Figure 2). There was                    Over the years, as our knowledge of the pathogenesis of pso-
no correlation between other genes’ expression levels and                   riasis has increased considerably, we know that it includes
PASI scores (Figures 3 and 4). In addition, there were no                   complex, multiple factors covering the genetic factors that
correlations between the expression levels of the genes and                 only explain about 70% of disease susceptibility [12]. Up
nail involvement, positive family history, and presence of                  to now, many single nucleotide polymorphism microarray
arthritis, either.                                                          and genome-wide association studies have been performed



4                                                                               Original Article | Dermatol Pract Concept. 2023;13(2):e2023085
                                                                                                                                P*=0.038
                                                                                                                                R=0.417
                   4.00




                   3.00
        SERPINB7




                   2.00




                   1.00

                                .0               10.0                   20.0                   30.0                      40.0
                                                                         PASI

        Figure 2. The correlation graph between SERPINB7 gene expression levels and PASI scores
        *P < 0.05.
        PASI = psoriasis area and severity index; SERPINB7 = serpin family B member 7.




                       12,00
                                                                                                                           P=0.639
                                                                                                                           R=0.098

                       10,00



                        8,00
               PTPN1




                        6,00



                        4,00



                        2,00



                          ,00

                                     ,0                 10,0                   20,0                   30,0                      40,0
                                                                                PASI

                   Figure 3. The correlation graph between PTPN1 gene expression levels and PASI scores (Spearman correlation).
                   PASI = psoriasis area and severity index; PTPN1 = tyrosine-protein phosphatase non-receptor type 1.


[13-15]. However, there is still a gap between genetic basis                   it was overexpressed in the spinous layer of the epidermis
and environmental triggers in pathogenesis. There have been                    of the psoriatic skin. Thus, they reported EREG might lead
many identified potential susceptibility genes for psoriasis,                  hyperproliferation of epidermis via possible intracellular sig-
and this discovery has been continued [8,13-15].                               naling systems such as STAT3 and may have essential for the
    Shirakata et al compared EREG gene expressions of 12                       development of psoriasis-like phenotype. In the same way,
psoriatic skin samples and 10 healthy skin samples [2]. They                   Iwata et al reported that the expression of EREG in dermal
observed that EREG mRNA was expressed very faintly in the                      fibroblasts was significantly upregulated approximately 50
basal layer of the epidermis of normal control skin, whereas                   times fold by co-stimulation with IL-17A and TNF-α, and



Original Article | Dermatol Pract Concept. 2023;13(2):e2023085                                                                              5
                                                                                                                  P=0.103
                                                                                                                  R=0.333
                   2,00




                   1,00
            EREG




                    ,00




                   -1,00

                           ,0                 10,0                    20,0                     30,0                    40,0
                                                                      PASI

            Figure 4. The correlation graph between EREG gene expression levels and PASI scores (Spearman correlation).
            EREG = epiregulin; PASI = psoriasis area and severity index.



this upregulation of EREG leads to keratinocyte prolifera-             which is an inhibitor of insulin signaling pathway in many
tion in vitro [16]. Thus, both study showed that EREG is a             studies [6,21-23]. In chronic inflammatory situations such
vital stimulator of keratinocyte proliferation which is cru-           as psoriasis, it was demonstrated that high levels of proin-
cial feature of immunopathogenesis of psoriasis as well. Al-           flammatory cytokines activate p38MAPK, which induces in-
though we could not show expression levels of the EREG                 sulin receptors, and leads to blockade of differentiation and
gene according to the layers of the skin, since it is known his-       hyperproliferation of basal keratinocytes. In addition, as a
topathologically that the spinous layer is hyperproliferated           result of the insulin receptor induction, much more insulin
in psoriasis [17], it might be thought that overexpression of          was produced than normal. This condition, called hyperin-
EREG gene seems to be related to this change. Our study                sulinemia, accelerates lipogenesis with increased production
supports these notions about EREG gene with the result of              of free fatty acids, though [24]. We know that psoriatic pa-
overexpressed EREG gene in the lesional skin of psoriatic              tients have a higher risk of having type 2 DM compared to
patients. Furthermore, the non-lesional skin of patients with          controls [25]. In addition, as mentioned before, the regula-
psoriasis has significantly down-regulated expression of the           tory effect of PTPN1 on Munc18c protein affects adipocytes
EREG gene than the healthy skin of controls, which may                 which are also attendant cells to the psoriasis pathogenesis
be caused by the migration of immune cells including fibro-            [24]. In our study we excluded the psoriatic patients who
blasts to the inflammation regions in the psoriatic patients.          also have systemic inflammatory diseases or conditions such
    In 2004, Shirasawa et al showed that EREG is expressed             as DM and hyperlipidemia, thus we did not evaluate the as-
not only in keratinocytes but also in tissue-resident macro-           sociation of psoriasis and them at all. However, since the
phages which are important cells for the immune balance in             expression of the PTPN1 gene was observed significantly up-
the skin.                                                              regulated in the lesional skin of patients compared to normal
    They claimed that EREG is physiologically a critical               skin of controls, there could be an underlying undiagnosed
molecule for tight regulation of IL-18 in keratinocytes and            insulin resistance or glucose intolerance conditions or altered
proper production of proinflammatory cytokines by macro-               lipid metabolism pathways in our patient group enrolled in
phages [18]. IL-18 belongs to IL-1 cytokine family that plays          the study.
a pathogenetically important role in chronic inflammatory                    Besides these, Yin et al evaluated the common genetic
conditions of skin such as psoriasis [19,20]. Therefore, we            factors shared between psoriasis and schizophrenia. Even
assume that upregulation of EREG gene causes hyperprolif-              though they reported that any common variant was not
eration of keratinocytes and chronic inflammation in psoria-           found between two diseases, they claimed that PTPN1 gene
sis via intracellular signaling pathways.                              may be a novel-susceptible gene for psoriasis which inter-
    Up to now, PTPN1 was shown as associated with dyslip-              acts with well-known susceptible genes for psoriasis such as
idemia, insulin resistance, type 2 DM, and obesity via PTP1B           NFKBA, STAT3, and TYK2 genes [7]. Similarly, we showed



6                                                                            Original Article | Dermatol Pract Concept. 2023;13(2):e2023085
significantly upregulated PTPN1 gene expression in the le-        with future studies. Even though our study is the only study
sional psoriatic skin than the non-lesional skin of the same      evaluating SERPINB7 gene in a high number of real patients
patients, and also healthy skin of controls. Moreover, to the     lesional, non-lesional skins and normal skins of healthy con-
best of our knowledge, the present study is the only study        trols, these findings need to be proven in further studies.
evaluating PTPN1 gene expression at the tissue layer. In ad-            With this study, we demonstrated that balanced function
dition, even though we have yet to learn very little about        of the EREG gene, decreased function of the PTPN1 gene,
how the PTPN1 gene causes psoriasis development, upregu-          and normal function of the SERPINB7 gene play a critical
lation of PTPN1 might lead to hyperproliferation of epider-       role in preventing the development of psoriasis. We believe
mis via STAT3 like EREG gene, and therefore, upregulated          that in the future, gene therapies that can even cure diseases
expression of PTPN1 gene has crucial roles in the psoriasis       will be more important than inhibiting the underlying in-
pathogenesis as well.                                             flammatory mechanism in chronic inflammatory diseases.
    A type of hereditary palmoplantar keratoderma (PPK)
with SERPINB7 gene mutations was identified by Kubo et
                                                                  Acknowledgement: This work was supported by scholarship
al and, they reported that mutations in the SERPINB7 gene
                                                                  from Turkish Dermatology Association.
cause alteration in the epithelium of the skin [4]. They also
claimed that the normal functioned SERPINB7 gene pro-
tects keratinocytes from oxidative stress-mediated cellular       References
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expression levels of SERPINB7 in the lesional skin of pso-
                                                                        mon PTPN1 gene variants in type 2 diabetes, obesity and asso-
riatic patients makes us think that SERPINB7 has protec-                ciated phenotypes in the French population. BMC Med Genet.
tive roles for many cells including keratinocytes. Shiba et             2006;7:44. DOI: 10.1186/1471-2350-7-44. PMID: 16677372.
al reported significant down-regulation of SERPINB7 gene                PMCID: PMC1525165.
expression in oral squamous cell carcinoma samples than            7.   Yin X, Lin Y, Shen C, et al. Integration of expression quantitative
                                                                        trait loci and pleiotropy identifies a novel psoriasis susceptibil-
in normal tissue samples which also supports our findings
                                                                        ity gene, PTPN1. J Gene Med. 2017;19(1-2):10.1002/jgm.2939.
about protective role of SERPINB7 gene [26]. Furthermore,
                                                                        DOI: 10.1002/jgm.2939. PMID: 27976820.
we also found a negative correlation between the severity          8.   Wang Z, Zheng H, Zhou H, et al. Systematic screening and iden-
of the disease and SERPINB7 gene expression levels. Nev-                tification of novel psoriasis‑specific genes from the transcriptome
ertheless, the contradictory results about SERPINB7 in the              of psoriasis‑like keratinocytes. Mol Med Rep. 2019;19(3):1529-
literature may be related to low number of tissue sample or             1542. DOI: 10.3892/mmr.2018.9782. PMID: 30592269. PM-
                                                                        CID: PMC6390042.
different methods of the studies such as cell culture, mice
                                                                  9.    Benezeder T, Painsi C, Patra V, et al. Dithranol targets kera-
tissues in vitro. Besides the protective roles of SERPINB7, it
                                                                        tinocytes, their crosstalk with neutrophils and inhibits the
also seems to be a marker of disease severity. We also think            IL-36 inflammatory loop in psoriasis. Elife. 2020;9:e56991.
that SERPINB7 might be showed as a determinant of prog-                 DOI: 10.7554/eLife.56991. PMID: 32484435. PMCID:
nosis and response to treatment in patients with psoriasis              PMC7266641.



Original Article | Dermatol Pract Concept. 2023;13(2):e2023085                                                                          7
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