A new animal model and cell lineages to investigate cancer-driver mutations in endometriosis

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22674
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
• Research Institution: Gunma University
• Principal Investigator: Iwase Akira 群馬大学, 大学院医学系研究科, 教授 (20362246)
• Co-Investigator(Kenkyū-buntansha): 平川 隆史 群馬大学, 大学院医学系研究科, 准教授 (80375534) ; 中村 智子 名古屋大学, 医学部附属病院, 講師 (40732681)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 子宮内膜症 / TCF21 / 線維化

Outline of Final Research Achievements

Immunohistochemistry (IHC) revealed that the expression of TCF21 is increased according to the development of endometriosis. IHC and in vitro analyses demonstrated that the TCF21-dependent pathway to induce periostin production and αSMA expression is involved in the local fibrosis of endometriosis. We also found that the IL-4, -13 and TGFβ are co-localized with TCF21 and that IL-4 upregulates the TGFβ-induced and TCF21-dependent production of periostin and αSMA. Taken together, TCF21-positive stromal cells play significant role in local fibrosis in endometriosis under local inflammatory response. Our results suggest that TCF21 can be a new therapeutic target for endometriosis.

Free Research Field

生殖医学

Academic Significance and Societal Importance of the Research Achievements

子宮内膜症は、疼痛、不妊症、がん発生母地となる重要な疾患である。局所炎症と線維化が重要な病態のひとつであるが、その分子メカニズムについては詳細が明らかではなかった。今回の研究で、TCF21陽性間質細胞が局所の線維化に関与すること、TCF21発現抑制により実験的には線維化が抑制されることが示され、TCF21が子宮内膜症の新たな治療ターゲットとなる可能性があるといえる。