C2C12成肌细胞通过由纤连蛋白2介导的TGF-β1信号通路分化为肌成纤维细胞。
C2C12 myoblasts differentiate into myofibroblasts via the TGF-β1 signaling pathway mediated by Fibulin2.
作者信息
Yang Yongqiang, Li Lei, Fei Jun, Li Zhong
机构信息
Department of Orthopaedics, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, PR China.
Department of Stem Cell and Regenerative Medicine, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, PR China.
出版信息
Gene. 2025 Feb 5;936:149048. doi: 10.1016/j.gene.2024.149048. Epub 2024 Oct 28.
Myoblasts play a critical role in the regeneration of skeletal muscle following injury. It has been reported that local elevation of transforming growth factor-β1 (TGF-β1) after skeletal muscle injury induces differentiation of myoblasts into myofibroblasts. However, the mechanisms underlying this differentiation process remain incompletely understood. In this study, we found that Fibulin2 expression significantly increases in myoblasts in response to TGF-β1 stimulation. Elevated Fibulin2 levels enhance the expression of fibrotic markers. Conversely, downregulation of Fibulin2 in myoblasts inhibits the upregulation of fibrotic markers induced by TGF-β1 stimulation. Extracellular secretion of Fibulin2 activates the TGF-β1-Smad2 pathway, thereby promoting the upregulation of fibrotic markers. Hence, Fibulin2 and TGF-β1 form a positive feedback loop that facilitates differentiation of myoblasts into myofibroblasts.
成肌细胞在骨骼肌损伤后的再生过程中发挥着关键作用。据报道，骨骼肌损伤后局部转化生长因子-β1（TGF-β1）水平升高会诱导成肌细胞分化为肌成纤维细胞。然而，这一分化过程的潜在机制仍未完全明确。在本研究中，我们发现，成肌细胞中Fibulin2的表达在TGF-β1刺激下显著增加。Fibulin2水平升高会增强纤维化标志物的表达。相反，成肌细胞中Fibulin2的下调会抑制TGF-β1刺激诱导的纤维化标志物上调。Fibulin2的细胞外分泌激活TGF-β1-Smad2信号通路，从而促进纤维化标志物的上调。因此，Fibulin2和TGF-β1形成了一个正反馈环，促进成肌细胞向肌成纤维细胞的分化。
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