Turkiye Klinikleri Journal of Dermatology

.: ORIGINAL RESEARCH
YAP/TAZ Sinyal Yolağının Mekanik Stres Kaynaklı Hipertrofik Skar Oluşumuna Etkisinin GEO2R ile Belirlenmesi: In Slico Analiz
Determination the Effect of YAP/TAZ Signaling Pathway on Mechanical Stress Induced Hypertrophic Scar Formation by GEO2R
Evin İŞCANa
aİzmir Biyotıp ve Genom Merkezi, İzmir, TÜRKİYE
bDokuz Eylül Üniversitesi İzmir Uluslararası Biyotıp ve Genom Enstitüsü, Biyotıp ve Sağlık Teknolojileri ABD, İzmir, TÜRKİYE
Turkiye Klinikleri J Dermatol. 2021;31(2):109-17
doi: 10.5336/dermato.2020-80691
Article Language: TR
ÖZET
Amaç: Hipertrofik skar travma, geçirilen ameliyatlar, yanık ve bazı cilt enfeksiyonları sonrası yaygın olarak görülebilen bir cilt sorunudur. Mevcut tedaviye verilen zayıf yanıt ve yüksek nüks oranları göz önüne alındığında hipertrofik skarların oluşumunun engellenmesinde hedeflenmiş, etkili topikal moleküler tedavi stratejilerinin belirlenmesine ve geliştirilmesine ihtiyaç vardır. YAP/TAZ, Hippo sinyal yolağı hedef molekülleridir. Bu çalışmada, mekanik stres kaynaklı hipertrofik skar oluşumunda rol alan YAP/TAZ hedef genlerinin belirlenmesi amaçlanmaktadır. Gereç ve Yöntemler: Mekanik stres kaynaklı hipertrofik skar oluşumunda rol oynayan genlerin ifade verisine 'Gene Expression Omnibus' veri tabanından erişildi. p<0,05 anlamlılık düzeyinde, 2 kat ve üzerinde değişim gösteren genlerin listesi oluşturuldu. Oluşturulan gen listesinde, YAP/TAZ sinyal yolağı hedef genleri belirlendi. Literatür taraması sonucunda, YAP/TAZ hedef genlerinin fonksiyonları belirlendi. Belirlenen genlerin etkileşim ağlarını ve rol oynadıkları sinyal yolaklarını bulmak için STRING protein etkileşim veritabanı kullanıldı. Bulgular: Anlamlı düzeyde değişim olan genlerin içinde YAP/TAZ sinyal yolağı hedef genlerinden; tenascin C, trombospondin 1, serin proteaz inhibitör 1'in ifadesinde artış gözlendi. Literatür taraması sonucunda bu genlerin yara iyileşmesi, hücre proliferasyonu, hücre farklılaşması ve hücre dışı matriksin yeniden yapılanmasında rol oynadıklarını gösterdik. Sonuç: Bu çalışmada, mekanik stres ile uyarılan hipertrofik skarlarda, YAP/TAZ sinyal iletim yolağının hedef genlerinin ifadesinin değiştiğini göstermiş bulunmaktayız. Hipertrofik skar oluşumunda YAP/TAZ sinyal yolağının rolünün belirlenmesine yönelik daha ileri çalışmaların yapılmasına ihtiyaç vardır.

Anahtar Kelimeler: Hipertrofik skar; YAP/TAZ sinyal iletim yolağı; GEO2R
ABSTRACT
Objective: Hypertrophic scar is a common skin problem after trauma, previous surgeries, burns and some skin infections. Considering the weak response and high recurrence rates linked to current treatments, it is necessary to determine and develop effective topical molecular treatment strategies which could prevent the formation of hypertrophic scar. YAP and TAZ are effector molecules of the Hippo signaling. In this study, it is aimed to determine the YAP/TAZ target genes involved in the formation of the mechanical stress-induced hypertrophic scar. Material and Methods: The gene expression data implicated in the formation of mechanical stress-induced Hypertrophic scar accessed from the Gene Expression Omnibus database. Genes with a 2-fold or more change at p<0.05 significance level were included in the list. YAP/TAZ signaling target genes were determined among the upregulated genes. The functions of YAP/TAZ target genes were determined by literature searching. STRING protein interaction database was used to find the interaction networks of the identified genes and the signal pathways in which they play a role. Results: Among the genes with significant changes, YAP/TAZ signaling target genes tenascin C, thrombospondin 1, serine protease inhibitor 1 expressions were increased. As a result of the literature review, we showed that these genes play a role in wound healing, cell proliferation, cell differentiation, and remodeling of the extracellular matrix. Conclusion: In this study, we have shown that the YAP/TAZ signaling plays a role in mechanical stress-induced hypertrophic scar and further studies are needed to determine its role in the formation of hypertrophic scar.

Keywords: Hypertrophic scar; YAP/TAZ signaling; GE02R
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