Downregulation of miR143/145 gene cluster expression promotes the aortic media degeneration process via the TGF-?1 signaling pathway.

ABSTRACT: Aortic dissection (AD) is a serious threat to human health; however, the cause of this condition has not yet been fully elucidated. In this study, we found significantly increased expression of phospho-Smad2/3 and phospho-ERK in AD tissues and downregulated expression of miR143 and miR145 in AD tissues. Knockdown of the miR143/145 gene cluster induced phenotypic switching of vascular smooth muscle cells (VSMCs) and activation of the TGF-?1 signaling pathway. When the TFG-?1 signaling pathway was blocked by pretreatment with an LY364947 inhibitor, expression of miR143 and miR145, and VSMC phenotypic markers were not affected by knockdown of the miR143/145 gene cluster. Immunohistochemical staining of aortic tissues donated by AD patients and organ donors showed decrease alpha-smooth muscle actin (?-SMA) expression in pathological tissue, while osteopontin (OPN) expression increased and the arrangement of smooth muscle cells in the tunica media was dysregulated. In conclusion, our study suggests that downregulated expression of the miR143/145 gene cluster promotes phenotypic switching of VSMCs via the TGF-?1 signaling pathway. This may play an important role in the pathogenesis of AD.

SUBMITTER: Zhang M 

PROVIDER: S-EPMC6357338 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature