2. Academic Validation
  3. Hsp70 Interacts with Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinase 2 To Regulate p38MAPK Stability and Myoblast Differentiation during Skeletal Muscle Regeneration

Hsp70 Interacts with Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinase 2 To Regulate p38MAPK Stability and Myoblast Differentiation during Skeletal Muscle Regeneration

  • Mol Cell Biol. 2018 Nov 28;38(24):e00211-18. doi: 10.1128/MCB.00211-18.
Wei Fan # 1 2 3,  Xiu Kui Gao # 1 2 3,  Xi Sheng Rao # 1 2 3,  Yin Pu Shi 1 2 3,  Xiao Ceng Liu 1 2 3,  Fei Ya Wang 4,  Yu Fen Liu 1 2 3,  Xiao Xia Cong 1 2 3,  Min Yi He 1 2 3,  Shui Bo Xu 1 2 3,  Wei Liang Shen 1 2 3,  Yue Shen 1 2,  Shi Gui Yan 1 2,  Yan Luo 1 2,  Boon Chuan Low 5,  Hongwei Ouyang 3 6,  Zhang Bao 7,  Li Ling Zheng 8 2 3 6,  Yi Ting Zhou 8 2 3 6
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou, China.
  • 2 Department of Orthopaedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 3 Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, China.
  • 4 Department of Pathology, Hospital of Pingdingshan Coal Industry Group, Pingdingshan, China.
  • 5 Mechanobiology Institute, Department of Biological Sciences, National University of Singapore, Singapore, Singapore.
  • 6 China Orthopedic Regenerative Medicine Group (CORMed), Hangzhou, China.
  • 7 Department of Respiratory Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 8 Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou, China zhengliling@zju.edu.cn zhouyt@zju.edu.cn.
  • # Contributed equally.
PMID: 30275345 DOI: 10.1128/MCB.00211-18
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.

Keywords

Hsp70/Hsc70; MAPKAPK2; muscle regeneration; myoblast differentiation; myogenesis; p38MAPK.

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