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.
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肌纤维坏死性凋亡通过在再生过程中释放腱蛋白-C 促进肌肉干细胞增殖
DOI：
10.1038/s41422-020-00393-6
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发表时间：
2020-12
期刊：
影响因子：
44.1
通讯作者：
Sun L
中科院分区：
文献类型：
--
作者：
Zhou S;Zhang W;Cai G;Ding Y;Wei C;Li S;Yang Y;Qin J;Liu D;Zhang H;Shao X;Wang J;Wang H;Yang W;Wang H;Chen S;Hu P;Sun L
坏死性凋亡是程序性细胞死亡的一种形式，其特征在于膜完整性的丧失和细胞内内容物的释放，其执行取决于混合谱系激酶结构域样蛋白（MLKL）在其磷酸化后的膜破坏活性。在这里，我们发现肌肉损伤后肌纤维发生MLKL依赖性坏死性凋亡。无论是药理学抑制坏死性凋亡上游激酶受体相互作用蛋白激酶1（RIPK 1）或基因消融MLKL表达的肌纤维导致显着的肌肉再生缺陷。通过将因子释放到肌肉干细胞（MuSC）微环境中，坏死性肌纤维促进肌肉再生。由坏死性下垂肌纤维释放的生腱蛋白-C（TNC）被发现对MuSC增殖至关重要。TNC在肌纤维中的临时表达受坏死性凋亡的严格控制; TNC的细胞外释放依赖于坏死性凋亡膜的破裂。TNC通过其N端组装结构域与EGF样结构域一起直接激活MuSC中的EGF受体（EGFR）信号通路。这些发现表明，坏死性凋亡在促进MuSC增殖以促进肌肉再生中起关键作用。
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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影响因子：
8
作者：
Fu, Xin;Wang, Huating;Hu, Ping
通讯作者：
Hu, Ping
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影响因子：
82.9
作者：
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影响因子：
8.8
作者：
Dondelinger, Yves;Declercq, Wim;Vandenabeele, Peter
通讯作者：
Vandenabeele, Peter
影响因子：
4.8
作者：
GHERZI, R;CARNEMOLLA, B;ZARDI, L
通讯作者：
ZARDI, L
影响因子：
1.2
作者：
Guardiola, Ombretta;Andolfi, Gennaro;Minchiotti, Gabriella
通讯作者：
Minchiotti, Gabriella