Elucidation of Wnt5a signal transduction mechanism(s) in keloid and application of molecular targeted therapy

2014 Fiscal Year Final Research Report

• Project/Area Number: 24592722
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Plastic surgery
• Research Institution: Nippon Medical School
• Principal Investigator: GHAZIZADEH MOHAMMAD 日本医科大学, 医学部, その他 (30190979)
• Co-Investigator(Kenkyū-buntansha): TOSA Mamiko 日本医科大学, 医学部, 助教 (30301568)
• Co-Investigator(Renkei-kenkyūsha): SHIMIZU Hajime 日本医科大学, 老人病研究所, マネージメントサポートスタッフ (60398873) ; MURAKAMI Masahiro 日本医科大学, 医学部, 准教授 (00239500)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: Keloid pathogenesis / Wnt5a / beta-catenin / EMT / Wnt signal-related genes / 分子標的治療

Outline of Final Research Achievements

We studied the expression and function of Wnt5a considering frizzled4 receptor, ROR2, Wnt signal downstream targets (GSK3-beta and beta-catenin) as well as epithelial-mesenchymal transition (EMT) markers and 84 Wnt signal-related genes in primary fibroblast cultures and tissue samples from keloid (KF) and normal dermis (NF)using molecular biology, immunohistochemical and RT2 Profiler PCR Array methods. A high expression of Wnt5a and beta-catenin was found in KF compared to NF. Treatment of NF and KF with recombinant Wnt5a peptide resulted in an increase in total beta-catenin and phosphorylated beta-catenin at Ser33/37/Thr41 but no significant change in phosphorylated beta-catenin at Ser45/Thr41 positions. Several Wnt signal-related genes were also upregulated. In addition, evidence for EMT in keloid was observed. These findings highlight a potential role for a Wnt/beta-catenin pathway triggered by Wnt5a in keloid pathogenisis and development of molecular targeted therapy for keloid.

Free Research Field

医歯薬学