1. Hsp70 Interacts with Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinase 2 To Regulate p38MAPK Stability and Myoblast Differentiation during Skeletal Muscle Regeneration
- Author
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Wei Fan, Zhang Bao, Wei Liang Shen, Hongwei Ouyang, Yan Luo, Yi Ting Zhou, Yin Pu Shi, Xiao Xia Cong, Yu Fen Liu, Li Ling Zheng, Yue Shen, Xiu Kui Gao, Boon Chuan Low, Xi Sheng Rao, Min Yi He, Fei Ya Wang, Shui Bo Xu, Shi Gui Yan, and Xiao Ceng Liu
- Subjects
0301 basic medicine ,p38 mitogen-activated protein kinases ,Down-Regulation ,Biology ,Protein Serine-Threonine Kinases ,Muscle Development ,p38 Mitogen-Activated Protein Kinases ,Cell Line ,Myoblasts ,03 medical and health sciences ,Mice ,medicine ,Myocyte ,Animals ,Regeneration ,HSP70 Heat-Shock Proteins ,Protein kinase A ,Muscle, Skeletal ,Molecular Biology ,Myogenesis ,Regeneration (biology) ,MAPKAPK2 ,Intracellular Signaling Peptides and Proteins ,Skeletal muscle ,Cell Differentiation ,Cell Biology ,musculoskeletal system ,Cell biology ,Up-Regulation ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Mitogen-activated protein kinase ,biology.protein ,Research Article - Abstract
The regenerative process of injured muscle is dependent on the fusion and differentiation of myoblasts derived from muscle stem cells. Hsp70 is important for maintaining skeletal muscle homeostasis and regeneration, but the precise cellular mechanism remains elusive. In this study, we found that Hsp70 was upregulated during myoblast differentiation. Depletion or inhibition of Hsp70/Hsc70 impaired myoblast differentiation. Importantly, overexpression of p38 mitogen-activated protein kinase α (p38MAPKα) but not AKT1 rescued the impairment of myogenic differentiation in Hsp70- or Hsc70-depleted myoblasts. Moreover, Hsp70 interacted with MK2, a substrate of p38MAPK, to regulate the stability of p38MAPK. Knockdown of Hsp70 also led to downregulation of both MK2 and p38MAPK in intact muscles and during cardiotoxin-induced muscle regeneration. Hsp70 bound MK2 to regulate MK2-p38MAPK interaction in myoblasts. We subsequently identified the essential regions required for Hsp70-MK2 interaction. Functional analyses showed that MK2 is essential for both myoblast differentiation and skeletal muscle regeneration. Taken together, our findings reveal a novel role of Hsp70 in regulating myoblast differentiation by interacting with MK2 to stabilize p38MAPK.
- Published
- 2018