Role of tenascin-X in progression of hepatic fibrosis and development of novel therapy

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08470
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Shimane University
• Principal Investigator: Matsumoto Ken-ichi 島根大学, 学術研究院医学・看護学系, 教授 (30202328)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 肝線維化 / テネイシンX / YAP / インテグリンalpha11beta1 / I型コラーゲン

Outline of Final Research Achievements

Tenascin-X (TNX), the largest member of the tenascin family, is involved in collagen deposition. So far, our group showed TNX allows inflammation and fibrosis in liver to get worse in mice fed a high-fat and high-cholesterol diet with high levels of phosphorus and calcium. In this project, I examined how TNX is involved in the aggravation of hepatic fibrosis by using the human hepatic stellate cell line LX-2 cells. I found out that the overexpression of a 15-amino acid peptide derived from the fibrinogen domain of TNX (hTNX-FGFFFF) with integrin alpha11 (ITGA11) induces the expression of type I collagen alpha1 chain (COL1A1). In addition, it was found that YAP (Yes-associate protein) signaling pathway participates in the induction of COL1A1 expression by the overexpression of hTNX-FGFFFF peptide with ITGA11. Accordingly, the suppression of the expression of hTNX-FGFFFF peptide might provide a novel therapeutic treatment for hepatic fibrosis.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

学術的意義：テネイシンファミリーのメンバーであるテネイシンCによる肝線維化亢進の報告は既にあったが、テネイシンX（TNX）に関しては本報告が初めてである。また、TNXの肝線維化亢進に関与する領域を15アミノ酸配列まで絞り込めたことは意義深い。また、TNXの肝維化亢進に関与する細胞内シグナル伝達機構として、Hippo/YAP経路が関与することが明らかとなったことは興味深い。社会的意義： 肝線維化亢進に関与するTNXフィブリノーゲン様領域由来15アミノ酸配列の領域の発現を抑制することによる肝線維化の新たな治療法の開発が期待できる。