New endoplasmic reticulum stress regulator, Gipie, regulates the survival of vascular smooth muscle cells and the neointima formation after vascular injury

Arteriosclerosis, Thrombosis, and Vascular Biology
Tomonori NodaToyoaki Murohara

Abstract

The accumulation of unfolded protein in the endoplasmic reticulum (ER) initiates an adaptive stress response, termed the unfolded protein response. Previous studies suggested that ER stress might be involved in the formation of neointima after vascular injury. We recently discovered a novel regulator of ER stress, 78-kDa glucose-regulated protein-interacting protein induced by ER stress (Gipie). The objective of this study was to elucidate the role of Gipie using models of vascular disease. We investigated the functions of Gipie in cultured vascular smooth muscle cells (VSMCs) and in a vascular injury model of a rat carotid artery. The expression of Gipie was predominantly detected in synthetic VSMCs and to a much lesser extent in contractile VSMCs, which was augmented by treatment with thapsigargin. Gipie knockdown increased the phosphorylation levels of c-Jun N-terminal kinase and the number of apoptotic cells under ER stress. Moreover, Gipie knockdown decreased the mature form of collagen I in synthetic VSMCs. The expression of Gipie was rarely detected in the medial VSMCs of the intact carotid artery, whereas it was detected in most of the neointimal cells and some of the medial VSMCs after balloon injury. Depletion of Gipi...Continue Reading

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Citations

Oct 19, 2016·Fundamental & Clinical Pharmacology·Wenting AiZuyi Yuan
Jun 2, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Sarah M PetersonLucy Liaw
Aug 12, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Qiang ZhaoJuan Zhou
Sep 24, 2020·Oxidative Medicine and Cellular Longevity·Shengjie YangSongzi Wang
Jun 8, 2021·Acta Pharmaceutica Sinica. B·Fen LongXinhua Liu

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