Asporin调控损伤骨骼肌内再生肌纤维功能分化及分子机制研究

doi:10.13418/j.issn.1001-165x.2026.1.08

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中国临床解剖学杂志 ›› 2026, Vol. 44 ›› Issue (1) : 48-52. DOI: 10.13418/j.issn.1001-165x.2026.1.08

实验研究

Asporin调控损伤骨骼肌内再生肌纤维功能分化及分子机制研究

王琪森¹，黄静雯¹，菅晓婷¹，赵子炜¹，桂炜超²，胡稷杰²*，廖华¹*

作者信息 +

Asporin mediates myofiber differentiation and the mechanism investigation after myoinjury

Wang Qisen¹, Huang Jingwen¹, Jian Xiaoting¹, Zhao Ziwei¹, Gui Weichao², Hu Jijie²*, Liao Hua¹*

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文章历史 +

摘要

目的探讨Asporin（ASPN）在骨骼肌损伤修复过程中的表达、功能效应及其分子机制。方法 Cardiotoxin（CTX）肌内注射制备急性肌损伤小鼠模型。ASPN重组蛋白（rmASPN）或中和抗体（anti-ASPN）肌内注射干预损伤肌内ASPN水平。肌损伤0、4、7、10 d取材，免疫荧光、Western blot 或 RT-qPCR检测 ASPN、肌转录因子（MyoD、Myogenin）、TGF-β/Smad2/3通路分子表达情况。Western blot 分析体外培养C2C12分化肌管 p-Smad2/3蛋白表达。结果生理状态下，肌纤维稳定表达ASPN蛋白。肌损伤炎性期（D4）及肌再生早期（D7）可见肌组织ASPN蛋白水平显著上调，Dystrophin阳性的中央核再生肌纤维高表达ASPN蛋白。 ASPN的表达随肌修复的完成而逐渐下调。rmASPN 处理可致再生肌纤维数量增加、面积增大，肌纤维MyoD、Myogenin 表达上调，但p-Smad2/3 表达降低。anti-ASPN 处理则与rmASPN结果相反。致炎刺激可诱导C2C12 肌管上调ASPN水平、但抑制p-Smad2/3蛋白表达。结论肌损伤后，再生肌纤维合成并分泌ASPN。炎性肌组织内ASPN蛋白可能干预并抑制肌纤维TGF-β-p-Smad2/3 通路激活，从而促进再生肌纤维的功能分化。

Abstract

Objective To investigate the expression, function and related molecular mechanisms of Asporin (ASPN) in the repair process of injuried skeletal muscle. Methods An acute muscle injury mice model was prepared by intramuscular injection of Cardiotoxin (CTX). For interfering in ASPN levels in injured muscle, the recombinant ASPN protein (rmASPN) or neutralizing antibody (anti-ASPN) was treated respectively. Muscle samples were collected on 0 d, 4 d, 7 d, and 10 d post myoinjury, and the expression of ASPN, muscle transcription factors (MyoD, Myogenin), and TGF-β/Smad2/3 pathway molecules were detected by immunofluorescence, Western blot, or RT-qPCR separately. In differentiated C2C12 myotubes cultured in vitro, Western blot was used to detect p-Smad2/3 protein. Results Under physiological condition, muscle fibers stably expressed ASPN protein. During the muscle inflammatory phase (D4) and early stage of muscle regeneration (D7), significant upregulation of ASPN protein was observed in muscle tissue, and in Dystrophin+ centra-nucleus regenerating myofibers. The level of ASPN gradually decreased with the completion of myorepair. rmASPN treatment induced the increase of number and area of regenerated myofibers, and upregulated MyoD and Myogenin levels, but decreased the level of p-Smad2/3 in myofibers. As expected, anti-ASPN treatment resulted in the opposite outcome. As well, inflammatory stimuli induced ASPN upregulation, but inhibited p-Smad2/3 expression in C2C12 myotubes. Conclusions After myoinjury, regenerated myofibers synthesize and secrete ASPN. In inflamed muscle, ASPN may intervene and inhibit the activation of TGF-β-p-Smad2/3 signaling in myofibers, thereby promoting the functional differentiation of regenerated myofibers.

导出引用

王琪森, 黄静雯, 菅晓婷, 赵子炜, 桂炜超, 胡稷杰, 廖华. Asporin调控损伤骨骼肌内再生肌纤维功能分化及分子机制研究[J]. 中国临床解剖学杂志. 2026, 44(1): 48-52 https://doi.org/10.13418/j.issn.1001-165x.2026.1.08

Wang Qisen, Huang Jingwen, Jian Xiaoting, Zhao Ziwei, Gui Weichao, Hu Jijie, Liao Hua. Asporin mediates myofiber differentiation and the mechanism investigation after myoinjury[J]. Chinese Journal of Clinical Anatomy. 2026, 44(1): 48-52 https://doi.org/10.13418/j.issn.1001-165x.2026.1.08

中图分类号： R322.74 R685.4

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