Induction of endometriotic cells by the upregulatory gene detected by the network analysis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09803
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Yamaguchi University
• Principal Investigator: Maekawa Ryo 山口大学, 医学部附属病院, 講師 (90598749)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 子宮内膜症 / HOXC8 / 疾患上流遺伝子

Outline of Final Research Achievements

The purpose of the study is to identify the upstream regulators (URs) involved in the onset and pathogenesis of ovarian endometrioma. We identified HOXC8 as a potential UR in ovarian endometrioma. HOXC8 overexpression significantly enhanced cell proliferation, migration, adhesion, and fibrotic activities, and altered expression statuses of the genes involved in transforming growth factor (TGF)-beta signaling. HOXC8 overexpression also increased the expression levels of phosphorylated SMAD2/SMAD3. The increased adhesion and fibrosis activities by HOXC8 were significantly inhibited by E-616452, a selective inhibitor of TGF-beta receptor type I kinases. Integrated genomic approaches identified HOXC8 as an UR in ovarian endometrioma. The pathological features of ovarian endometrioma including cell proliferation, adhesion, and fibrosis were induced by HOXC8 and its subsequent activation of TGF-beta signaling.

Free Research Field

子宮内膜症

Academic Significance and Societal Importance of the Research Achievements

本研究において、疾患発症に重要な遺伝子としてHOXC8を同定し、HOXC8がTGFβシグナリングを活性化させて、増殖、浸潤、癒着、線維化能を実際に促進することを証明した。本研究により、根治的な治療法が存在しない子宮内膜症において、将来的にこの遺伝子を標的とした治療法の開発に発展する可能性がある。