WNT5A drives interleukin-6-dependent epithelial-mesenchymal transition via the JAK/STAT pathway in keloid pathogenesis

作     者：Young In Lee Jung Eun Shim Jihee Kim Won Jai Lee Jae Woo Kim Kee Hyun Nam Ju Hee Lee 

作者机构：Department of DermatologySeverance HospitalCutaneous Biology Research InstituteYonsei University College of MedicineSeoul 03722Korea Bioinformatics Collaboration UnitYonsei University College of MedicineSeoul 03722Korea Department of Plastic and Reconstructive SurgerySeverance HospitalYonsei University College of MedicineSeoul 03722Korea Scar Laser and Plastic Surgery CenterYonsei Cancer HospitalYonsei University College of MedicineSeoul 03722Korea Department of Biochemistry and Molecular BiologyChronic Intractable Disease for Systems Medicine Research CenterYonsei University College of MedicineSeoul 03722Korea Department of SurgerySeverance HospitalYonsei University College of MedicineSeoulKorea 

出 版 物：《Burns & Trauma》 (烧伤与创伤（英文）)

年 卷 期：2022年第10卷第1期

页      面：200-215页

核心收录：

学科分类：1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

基　　金：supported by the Health Fellowship Foundation Seoul Korea 

主　　题：Keloid Wnt family member 5A Interleukin-6 JAK/STAT pathway Epithelial-mesenchymal transition Scar Epithelial mesenchymal transition 

摘      要：Background:Keloid scarring is a fibroproliferative disease caused by aberrant genetic activation with an unclear underlying *** predisposition,aberrant cellular responses to environmental factors,increased inflammatory cytokines and epithelial-mesenchymal transition(EMT)phenomena are known as major *** this study,we aimed to identify the molecular drivers that initiate keloid ***:Bulk tissue RNA sequencing analyses of keloid and normal tissues along with ex vivo and in vitro tests were performed to identify the contributing genes to keloid *** animal model of inflammatory keloid scarring was reproduced by replication of a skin fibrosis model with intradermal bleomycin injection in C57BL/6 ***:Gene set enrichment analysis revealed upregulation of Wnt family member 5A(WNT5A)expression and genes associated with EMT in keloid ***,human keloid tissues and the bleomycin-induced skin fibrosis animal model showed significantly increased expression ofWNT5A and EMT *** activation of the interleukin(IL)-6/Janus kinase(JAK)/signal transducer and activator of transcription(STAT)pathway and subsequent elevation of EMT markerswas also observed in keratinocytes co-cultured withWNT5A-activated fibroblasts or keloid ***,WNT5A silencing and the blockage of IL-6 secretion via neutralizing IL-6 antibody reversed hyperactivation of the STAT pathway and EMT markers in ***,STAT3 silencing significantly reduced the EMT-like phenotypes in both keratinocytes and IL-6-stimulated ***:Intercellular communication via the WNT5A and STAT pathways possibly underlies a partial mechanism of EMT-like phenomena in keloid ***-6 secreted from WNT5A-activated fibroblasts or keloid fibroblasts activates the JAK/STAT signaling pathway in adjacent keratinocytes which in turn express EMT markers.A better understanding of keloid development and the