1. Academic Validation
  2. TGM2 positively regulates myoblast differentiation via enhancing the mTOR signaling

TGM2 positively regulates myoblast differentiation via enhancing the mTOR signaling

  • Biochim Biophys Acta Mol Cell Res. 2022 Mar;1869(3):119173. doi: 10.1016/j.bbamcr.2021.119173.
Dongdong Wang 1 Dandan Zhao 1 Yuan Li 2 Tingjun Dai 1 Fuchen Liu 1 Chuanzhu Yan 3
Affiliations

Affiliations

  • 1 Research Institute of Neuromuscular and Neurodegenerative Diseases, Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, People's Republic of China.
  • 2 Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, People's Republic of China.
  • 3 Research Institute of Neuromuscular and Neurodegenerative Diseases, Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, People's Republic of China; Mitochondrial Medicine Laboratory, Qilu Hospital (Qingdao), Shandong University, Qingdao 266035, Shandong, People's Republic of China; Brain Science Research Institute, Shandong University, Jinan 250012, Shandong, People's Republic of China. Electronic address: czyan@sdu.edu.cn.
Abstract

Myoblast differentiation is an essential process for the control of muscle regeneration. However, the intrinsic mechanisms underlying this dynamic process are still not well clarified. Herein, we identified transglutaminase type 2 (TGM2) as a novel regulator of muscle differentiation and regeneration in vitro and in vivo. Specifically, knockdown of TGM2 suppresses whereas overexpression of TGM2 promotes myoblast differentiation in differentiating C2C12 cells. Mechanistic studies revealed that TGM2 promotes C2C12 myoblast differentiation via enhancing GPR56 mediated activation of the mTOR signaling. Additionally, lentivirus mediated knockdown of TGM2 hinders the regeneration of muscles in a BaCl2 induced skeletal muscle injury model of mice. Finally, we found that both TGM2 and activation of the mTOR signaling are up-regulated in muscles of patients with immune-mediated necrotizing myopathy (IMNM), especially in the regenerating myofibers. Collectively, our research demonstrates that TGM2 positively regulates muscle differentiation and regeneration through facilitating the myogenic mTOR signaling, which might be a potential target of therapy for skeletal muscle injury.

Keywords

C2C12; GPR56; Muscle regeneration; Myoblast differentiation; TGM2; mTOR.

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