Umbilical cord mesenchymal stem cell-derived exosomal Follistatin inhibits fibrosis and promotes muscle regeneration in mice by influencing Smad2 and AKT signaling

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research Pub Date : 2025-01-15 DOI:10.1016/j.yexcr.2024.114396

Hai Hu , Yuesong Yin , Hecheng Zhou , Binbin Jiang , Ting Cai , Song Wu , Shuangfei Guo

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Abstract

Background

Promoting muscle regeneration through stem cell therapy has potential risks. We investigated the effect of umbilical cord mesenchymal stem cells (UMSCs) Exosomes (Exo) Follistatin on muscle regeneration.

Methods

The Exo was derived from UMSCs cells and was utilized to affect the mice muscle injury model and C2C12 cells myotubes atrophy model. The Western blot, qRT-PCR and IF were utilized to determine the effects of Exo on the levels of Follistatin, MyHC, MyoD, Myostatin, MuRF1, MAFbx, α-SMA, Collagen I, Smad2, and AKT. In addition, HE and Masson staining were used to assess muscle tissue damage in mice.

Results

The level of Follistatin in Exo was significantly higher than that in UMSCs. UMSCs-Exo increased the levels of Follistatin, MyHC, MyoD, and p-Smad2 and decreased the levels of Myostatin, MuRF1, MAFbx, α-SMA, Collagen I, p-AKT, and p-mTOR in mice or C2C12 cells. In addition, UMSCs-Exo decreased levels of inflammation and fibrosis in mice. However, UMSCs-Exo-si-Follistatin reversed the effect of UMSCs-Exo. Transfection of oe-Smad2 up-regulated the protein levels of Collagen I, α-SMA, and changed the ratio of p-Smad2/Smad2 expression to 0.33, and 0.34, 0.73. LY294002 decreased the levels of MyHC, MyoD, and the ratio of p-AKT/AKT and p-mTOR/mTOR expression to 0.12, 0.17, 0.33, and 0.41, increased the levels of MuRF1 and MAFbx to 0.36 and 0.34.

Conclusion

This study demonstrated that Follistatin in UMSCs-Exo inhibits fibrosis and promotes muscle regeneration in mice by regulating Smad and AKT signaling.

Abstract Image

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脐带间充质干细胞来源的外泌体Follistatin通过影响Smad2和AKT信号传导抑制小鼠纤维化并促进肌肉再生。

背景：通过干细胞治疗促进肌肉再生具有潜在的风险。我们研究了脐带间充质干细胞（UMSCs）外泌体（Exo）卵泡素对肌肉再生的影响。方法：从UMSCs细胞中提取Exo，应用于小鼠肌肉损伤模型和C2C12细胞肌管萎缩模型。采用western blot、qRT-PCR和IF检测Exo对细胞中Follistatin、MyHC、MyoD、Myostatin、MuRF1、MAFbx、α-SMA、Collagen I、Smad2和AKT水平的影响。此外，采用HE和Masson染色评估小鼠肌肉组织损伤。结果：Exo细胞中Follistatin水平明显高于UMSCs。UMSCs-Exo增加了小鼠或C2C12细胞中Follistatin、MyHC、MyoD和p-Smad2的水平，降低了Myostatin、MuRF1、MAFbx、α-SMA、Collagen I、p-AKT和p-mTOR的水平。此外，UMSCs-Exo降低了小鼠的炎症和纤维化水平。然而，UMSCs-Exo-si- follistatin逆转了UMSCs-Exo的作用。转染e-Smad2可上调α-SMA、I型胶原蛋白的表达水平，p-Smad2/Smad2的表达比分别为0.33、0.34、0.73。LY294002使MyHC、MyoD水平降低，p-AKT/ AKT和p-mTOR/mTOR表达比分别为0.12、0.17、0.33和0.41，MuRF1和MAFbx表达比分别为0.36和0.34。结论：本研究表明UMSCs-Exo中的Follistatin通过调节Smad和AKT信号通路抑制小鼠纤维化，促进肌肉再生。

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来源期刊

Experimental cell research 医学-细胞生物学

CiteScore

7.20

自引率

0.00%

发文量

295

审稿时长

30 days

期刊介绍： Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.