2. Academic Validation
  3. Myofiber necroptosis promotes muscle stem cell proliferation via releasing Tenascin-C during regeneration

Myofiber necroptosis promotes muscle stem cell proliferation via releasing Tenascin-C during regeneration

  • Cell Res. 2020 Dec;30(12):1063-1077. doi: 10.1038/s41422-020-00393-6.
Shen'ao Zhou 1 2,  Wei Zhang 1 2,  Gaihong Cai 3,  Yingzhe Ding 4 5,  Caixia Wei 1,  Sheng Li 1,  Yu Yang 1 2,  Jie Qin 1,  Dan Liu 1,  Hao Zhang 6,  Xiexiang Shao 7,  Jianhua Wang 7,  Hongye Wang 1,  Wenjun Yang 1,  Huating Wang 4 8,  She Chen 3 9,  Ping Hu 10 11 12 13 14 15,  Liming Sun 16 17 18
Affiliations

Affiliations

  • 1 State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
  • 2 University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 3 National Institute of Biological Sciences, 7 Science Park Road, Zhongguancun Life Science Park, Beijing, 102206, China.
  • 4 Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, 999077, Hong Kong SAR, China.
  • 5 Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, 999077, Hong Kong SAR, China.
  • 6 Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 7 Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
  • 8 Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, 999077, Hong Kong SAR, China.
  • 9 Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing 102206, China.
  • 10 State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China. hup@sibcb.ac.cn.
  • 11 University of Chinese Academy of Sciences, Beijing, 100049, China. hup@sibcb.ac.cn.
  • 12 Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China. hup@sibcb.ac.cn.
  • 13 Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, Guangdong, 510005, China. hup@sibcb.ac.cn.
  • 14 Bio-Research Innovation Center, Shanghai Institute of Biochemistry and Cell Biology, Suzhou, Jiangsu, 215121, China. hup@sibcb.ac.cn.
  • 15 Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai, 200120, China. hup@sibcb.ac.cn.
  • 16 State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China. liming.sun@sibcb.ac.cn.
  • 17 University of Chinese Academy of Sciences, Beijing, 100049, China. liming.sun@sibcb.ac.cn.
  • 18 Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China. liming.sun@sibcb.ac.cn.
PMID: 32839552 DOI: 10.1038/s41422-020-00393-6
Abstract

Necroptosis, a form of programmed cell death, is characterized by the loss of membrane integrity and release of intracellular contents, the execution of which depends on the membrane-disrupting activity of the Mixed Lineage Kinase Domain-Like protein (MLKL) upon its phosphorylation. Here we found myofibers committed MLKL-dependent Necroptosis after muscle injury. Either pharmacological inhibition of the Necroptosis upstream kinase Receptor Interacting Protein Kinases 1 (RIPK1) or genetic ablation of MLKL expression in myofibers led to significant muscle regeneration defects. By releasing factors into the muscle stem cell (MuSC) microenvironment, necroptotic myofibers facilitated muscle regeneration. Tenascin-C (TNC), released by necroptotic myofibers, was found to be critical for MuSC proliferation. The temporary expression of TNC in myofibers is tightly controlled by necroptosis; the extracellular release of TNC depends on necroptotic membrane rupture. TNC directly activated EGF receptor (EGFR) signaling pathway in MuSCs through its N-terminus assembly domain together with the EGF-like domain. These findings indicate that Necroptosis plays a key role in promoting MuSC proliferation to facilitate muscle regeneration.

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