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Induction of GLI1 by miR-27b-3p/FBXW7/KLF5 pathway contributes to pulmonary arterial hypertension.

Authors :
Wang, Qingting
Chai, Limin
Zhang, Qianqian
Wang, Jian
Liu, Jin
Chen, Huan
Wang, Yan
Chen, Yuqian
Shen, Nirui
Xie, Xinming
Li, Manxiang
Source :
Journal of Molecular & Cellular Cardiology. Oct2022, Vol. 171, p16-29. 14p.
Publication Year :
2022

Abstract

Glioma-associated oncogene homolog 1 (GLI1), a zinc-finger transcription factor, is upregulated in tumors and promotes cancer cell proliferation and migration. However, whether GLI1 involves in pulmonary artery smooth muscle cells (PASMCs) proliferation and migration and the detailed molecular mechanisms underlying GLI1 in pulmonary arterial hypertension (PAH) are not yet clear. Primary cultured rat PASMCs and monocrotaline (MCT)-induced PAH rats model were applied to address these issues in the present study. We found that the expression of GLI1 was significantly increased in endothelin-1 (ET-1) treated PASMCs, accompanied with the activation of microRNA (miR)-27b-3p/F-box and WD repeat domain containing 7 (FBXW7)/kruppel-like factor 5 (KLF5)/GLI1 pathway through endothelin-1 receptor type A (ETAR). Elevated miR-27b-3p suppressed FBXW7 expression, which led to KLF5 accumulation by decreasing its ubiquitinated degradation, KLF5 further induced GLI1 upregulation leading to PASMCs proliferation and migration. In addition, in MCT-induced PAH rats, targeting ETAR/miR-27b-3p/FBXW7/KLF5/GLI1 pathway effectively prevented the pulmonary vascular remodeling and the development of PAH in rats. Our study indicates that interfering ETAR/miR-27b-3p/FBXW7/KLF5/GLI1 signaling axis might have a potential value in the prevention and treatment of PAH. [Display omitted] • Increased GLI1 contributes to PASMCs proliferation and migration. • The miR-27b-3p/FBXW7/KLF5 axis mediates GLI1 upregulation in PAH. • Inhibiting ETAR/miR-27b-3p/FBXW7/KLF5/GLI1 pathway benefit PAH. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00222828
Volume :
171
Database :
Academic Search Index
Journal :
Journal of Molecular & Cellular Cardiology
Publication Type :
Academic Journal
Accession number :
159571436
Full Text :
https://doi.org/10.1016/j.yjmcc.2022.06.012