Department of Clinical Nursing, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, People's Republic of China.
Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, People's Republic of China.
Stem Cells. 2023 Oct 8;41(10):928-943. doi: 10.1093/stmcls/sxad053.
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 cells. Results showed that hucMSCs were retained in lung and hucMSCs treatment alleviated pulmonary fibrosis. Morphological staining indicated that hucMSCs-treated mice had thinner alveolar walls, effectively improved alveolar structure, significantly reduced alveolar inflammation, and decreased collagen deposition than control mice. Fibrotic proteins, including vimentin, α-SMA, collagens I and III, and the differentiation-related protein S100 calcium-binding protein A4 was 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.
本研究旨在探讨人脐带间充质干细胞（hucMSCs）治疗对肺纤维化的影响，并研究 hucMSCs 治疗的 circFOXP1 介导的自噬机制。通过向小鼠肺部喷洒博来霉素和 TGF-β1 处理 MRC-5 细胞建立肺纤维化模型。结果表明，hucMSCs 可在肺部中被保留，且 hucMSCs 治疗可减轻肺纤维化。形态学染色表明，与对照组小鼠相比，hucMSCs 治疗组小鼠的肺泡壁更薄，肺泡结构得到有效改善，肺泡炎症明显减轻，胶原沉积减少。纤维化蛋白，包括波形蛋白、α-SMA、I 型和 III 型胶原以及分化相关蛋白 S100 钙结合蛋白 A4，在 hucMSCs 治疗组中显著减少。机制研究表明，hucMSCs 治疗对肺纤维化的抑制作用依赖于下调 circFOXP1，其中 hucMSCs 治疗通过阻断核人抗原 R（HuR）易位并促进 HuR 降解，从而显著减少自噬负调节因子 EZH2、STAT1 和 FOXK1，促进 circFOXP1 介导的自噬过程。总之，hucMSCs 治疗通过下调 circFOXP1-HuR-EZH2/STAT1/FOXK1 自噬轴显著改善了肺纤维化。hucMSCs 可作为肺纤维化的有效治疗方法。
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