Endoplasmic Reticulum Stress Is Involved in Muscular Pathogenesis in Idiopathic Inflammatory Myopathies

Xue Ma; Hua-Jie Gao; Qing Zhang; Meng-Ge Yang; Zhua-Jin Bi; Su-Qiong Ji; Yue Li; Li Xu; Bi-Tao Bu

doi:10.3389/fcell.2022.791986

Endoplasmic Reticulum Stress Is Involved in Muscular Pathogenesis in Idiopathic Inflammatory Myopathies

Front Cell Dev Biol. 2022 Feb 14:10:791986. doi: 10.3389/fcell.2022.791986. eCollection 2022.

Authors

Xue Ma¹, Hua-Jie Gao¹, Qing Zhang¹, Meng-Ge Yang¹, Zhua-Jin Bi¹, Su-Qiong Ji¹, Yue Li¹, Li Xu¹, Bi-Tao Bu¹

Affiliation

¹ Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Abstract

Objectives: Endoplasmic reticulum (ER) stress plays pivotal roles in the regulation of skeletal muscle damage and dysfunction in multiple disease conditions. We postulate the activation of ER stress in idiopathic inflammatory myopathies (IIM). Methods: Thirty-seven patients with immune-mediated necrotizing myopathy (IMNM), 21 patients with dermatomyositis (DM), 6 patients with anti-synthetase syndrome (ASS), and 10 controls were enrolled. The expression of ER stress-induced autophagy pathway was detected using histological sections, Western blot, and real-time quantitative Polymerase Chain Reaction. Results: ER stress-induced autophagy pathway was activated in biopsied muscle of patients with IMNM, DM, and ASS. The ER chaperone protein, glucose-regulated protein 78 (GRP78)/BiP expression in skeletal muscle correlated with autophagy, myofiber atrophy, myonecrosis, myoregeneration, and disease activity in IMNM. Conclusion: ER stress was involved in patients with IIM and correlates with disease activity in IMNM. ER stress response may be responsible for skeletal muscle damage and repair in IIM.

Keywords: endoplasmic reticulum stress; glucose-regulated protein 78 (GRP78)/BiP; idiopathic inflammatory myopathies; immune-mediated necrotizing myopathy; skeletal muscle dysfunction.