The investigation on the involvement of TGF-beta signal transduction in fibrosis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10165
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kumamoto University
• Principal Investigator: IHN HIRONOBU 熊本大学, 大学院生命科学研究部(医), 教授 (20282634)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 遺伝子 / 細胞・組織 / シグナル伝達

Outline of Final Research Achievements

We identified the molecules up-regulated or down-regulated with cDNA microarray analyses using skin sections and cultured dermal fibroblasts from patients with systemic sclerosis (SSc). We also identified microRNAs up-regulated or down-regulated with microRNA array analyses in SSc. We identified the such molecules in integrinαVβ5 stable transfectants and TSP-1 stable transfectants. And we investigated the function of these microRNAs. We established TSP-1 transgenic mice using collagen promoter/ enhancer, and confirmed the extent of the over-expression of it in each organ. We investigated the skin, lung, and liver histologically, and inverstigated the expression of various molecules. And we investigated the existence of M2 macrophagesand the expression of B cell markers, Th2 cytokine, and interleukin-17

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

線維化の機序は未だ明らかでなく、線維化の治療も未だ確立せず、本邦においても、世界中でも多くの方が線維化を伴う疾患に罹患し、苦しみ、また結果として死を迎えている。線維化は、TGFβおよびTGFβ情報伝達の関与が考えられているが、その詳細は明らかではない。本研究により、線維化に対するTGFβ情報伝達の関与が詳細に明らかになれば、線維化治療のターゲット明らかになり、線維化治療法の開発が進み、学術的にも社会的にも大きなインパクトがある。