RhoGDI stability is regulated by SUMOylation and ubiquitination via the AT1 receptor and participates in Ang II-induced smooth muscle proliferation and vascular remodeling

Atherosclerosis
Fan DaiWenjuan Yao

Abstract

The physiological role of Rho-specific guanine nucleotide dissociation inhibitor (RhoGDI) in vascular remodeling remains unknown. We investigated the function of RhoGDI in angiotensin II (Ang II)-induced vascular remodeling in cultured human aortic vascular smooth muscle cells (HA-VSMCs) and in an Ang II-infusion vascular remodeling mouse model. For in vitro assays of HA-VSMCs, proliferation was assessed by BrdU and EdU assays and immunofluorescence analysis of ki-67 expression. RhoGDI1 and RhoGDI2 function and expression were assessed by RNAi, Western blotting and real-time RT-PCR. RhoGDI ubiquitination and SUMOylation levels were evaluated by co-immunoprecipitation and Western blotting. The functions of proteosomal-mediated degradation, ubiquitination, SUMOylation and Ang II receptors were assessed using specific inhibitors. To evaluate the in vivo effects of Ang II and RhoGDI, H & E staining, Masson's trichrome staining, and immunostaining were employed. Ang II treatment of HA-VSMCs for 6 or 48 h promoted RhoGDI1 and RhoGDI2 protein degradation and reduced cell proliferation, which was reversed by proteosome inhibition. In contrast, treatment with Ang II for 12 or 24 h induced dose-dependent cell proliferation without affect...Continue Reading

Citations

Nov 20, 2019·Journal of Cellular and Molecular Medicine·Yuqin WangZhaoguo Liu
Sep 8, 2019·Cells·Hee Jun ChoHee Gu Lee
May 23, 2020·Clinica Chimica Acta; International Journal of Clinical Chemistry·Yi-Zhang LiuChi Zhang

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