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

• 来源期刊: 细胞研究（英文版）
• 年，卷（期）: 2020,（12）
• 所属期刊栏目: ARTICLES
• 页码范围: 1063-1077
• 页数: 15页
• 语种: 英文

摘要

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.