hucMSCs treatment ameliorated pulmonary fibrosis via downregulating the circFOXP1-HuR-EZH2/STAT1/FOXK1 autophagic axis.
Stem cells (Dayton, Ohio)(2023)
摘要
This study was performed to determine the effect of human umbilical cord mesenchymal stem cells (hucMSCs) treatment on pulmonary fibrosis and investigate the circFOXP1-mediated autophagic mechanism of hucMSCs treatment. Pulmonary fibrosis models were established by spraying bleomycin in mice and TGF-β1 treatment of MRC-5 cell. Results showed that hucMSCs were retained in lung and hucMSCs treatment alleviated pulmonary fibrosis. Morphological staining indicated that hucMSCs-treated mice had thinner alveolar wall, effectively improved alveolar structure, significantly reduced alveolar inflammation, and decreased collagen deposition than control mice. Fibrotic proteins, including vimentin, α-SMA, collagen I, and collagen III, and the differentiation-related protein S100 calcium binding protein A4 were reduced considerably in the hucMSCs-treated group. The mechanistic study revealed that the inhibition of hucMSCs treatment on pulmonary fibrogenesis depended on downregulating circFOXP1, in which hucMSCs treatment promoted circFOXP1-mediated autophagy process via blocking the nuclear human antigen R (HuR) translocation and promoting the HuR degradation, leading to a marked decrease in autophagy negative regulators EZH2, STAT1 and FOXK1. In conclusion, hucMSCs treatment significantly improved pulmonary fibrosis by downregulating the circFOXP1-HuR-EZH2/STAT1/FOXK1 autophagic axis. hucMSCs can act as an effective treatment for pulmonary fibrosis.
更多查看译文
关键词
fibrosis,circfoxp1-hur-ezh2/stat1/foxk1
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要