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

Tomonori Noda, Kengo Maeda, Shinji Hayano, Naoya Asai, Atsushi Enomoto, Masahide Takahashi, Toyoaki Murohara

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Objective - 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. Approach and Results - 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 Gipie in the rat carotid artery attenuated the neointimal thickening, which was accompanied by increased cell death in the neointima. Conversely, overexpression of Gipie augmented the neointimal thickening. Conclusions - Gipie participates in the ER stress response in VSMCs and plays an important role in neointima formation after vascular injury.

Original languageEnglish
Pages (from-to)1246-1253
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume35
Issue number5
DOIs
Publication statusPublished - 27-05-2015

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'New endoplasmic reticulum stress regulator, gipie, regulates the survival of vascular smooth muscle cells and the neointima formation after vascular injury'. Together they form a unique fingerprint.

  • Cite this