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Gen Physiol Biophys. 2019 Jul;38(4):271-280. doi: 10.4149/gpb_2019017. Epub 2019 Jun 20.

ROCK inhibitors alleviate myofibroblast transdifferentiation and vascular remodeling via decreasing TGFβ1-mediated RhoGDI expression.

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1
Department of Pharmacology, School of Pharmacy, Nantong University, 19 QiXiu Road, Nantong, China. yaowenjuan0430@aliyun.com.

Abstract

The aim of this study was to investigate the effects of the Rho GDP dissociation inhibitor (RhoGDI) on TGFβ1-mediated vascular adventitia myofibroblast transdifferentiation and on the inhibition of ROCK inhibitors. Myofibroblast transdifferentiation and vascular remodeling model were induced by TGFβ1 in vitro and by balloon injury in vivo. H&E (Hematoxylin & Eosin) and PSR (Picrosirius Red) staining were used to observe vascular morphology while immunofluorescence, immunohistochemistry, and Western blotting were used to measure protein expression. Fasudil treatment reduced the expression of TGFβ1, RhoGDI1, and RhoGDI2 in addition to vascular remodeling in the rat balloon injury model. TGFβ1 induced the expression of α-SMA, TGFβRI, phospho-TGFβRI, RhoGDI1, RhoGDI2, and collagen secretion in human aortic adventitial fibroblasts (HAAFs). These effects were diminished after treatment with Y27632. Suppressing both RhoGDI1 and RhoGDI2 expression also blocked TGFβ1-induced α-SMA expression and collagen secretion in HAAFs. Moreover, TGFβR inhibition blocked TGFβ1-mediated collagen secretion and the expression of α-SMA, RhoGDI1, and RhoGDI2. These data suggested that ROCK inhibitors alleviate myofibroblast transdifferentiation and vascular remodeling by decreasing TGFβ1-mediated expression of RhoGDI.

PMID:
31219429
DOI:
10.4149/gpb_2019017

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