The mechanism of smooth muscle differentiation induced by ubiquitin-like modification in pulmonary hypertension

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K08508
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Gunma University
• Principal Investigator: Kawai-Kowase Keiko 群馬大学, 大学院医学系研究科, 教授 (50594264)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 肺高血圧 / 血管平滑筋

Outline of Final Research Achievements

This study aimed to clarify the mechanism of PIAS1 and SUMOylation from the viewpoint of dysregulation of vascular smooth muscle cell differentiation induction in the onset and progression of pulmonary arterial hypertension. In a pulmonary hypertension model mouse, we clarified the expression of PIAS1 with SUMOylation E3 ligase activity and the E2 enzyme ubc9 in the pulmonary artery of pulmonary hypertension. We demonstrated the possibility that PIAS1 is involved in the induction of smooth muscle differentiation markers by TGFbeta in PASMC. We also demonstrated that SUMOylation signals such as PIAS1 and ubc9, as well as Notch signaling, are involved in the induction of expression of OPG, a vascular calcification factor, and that SUMOylation may be involved in the induction of OPG expression and the suppression of Runx2 and Msx2 expression by FGF23.

Free Research Field

循環器

Academic Significance and Societal Importance of the Research Achievements

特発性肺動脈高血圧症(IPAH)などの肺動脈高血圧症(PAH)は、稀ではあるが、重篤な疾患である。その病態として、肺血管内皮細胞の機能障害により、血管拡張因子と血管収縮因子のバランスが破綻していることが知られている。このため、肺血管の持続的な攣縮や血管平滑筋細胞の増殖、肺動脈内での微少血栓形成が惹起され、肺高血圧の進展につながっていると考えられる。今回、私達は、肺高血圧において、血管平滑筋の形質変換という観点から、PIAS1/SUMO化の役割を明らかにすることを目的とした。また同時に、OPGや炎症性サイトカインに対する役割も検討した。