PMID- 37419489 OWN - NLM STAT- MEDLINE DCOM- 20231009 LR - 20231018 IS - 1549-4918 (Electronic) IS - 1066-5099 (Linking) VI - 41 IP - 10 DP - 2023 Oct 8 TI - hucMSCs Treatment Ameliorated Pulmonary Fibrosis via Downregulating the circFOXP1-HuR-EZH2/STAT1/FOXK1 Autophagic Axis. PG - 928-943 LID - 10.1093/stmcls/sxad053 [doi] AB - 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-beta1 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, alpha-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. CI - (c) The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com. FAU - Li, Ruiqiong AU - Li R AD - Department of Clinical Nursing, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, People's Republic of China. FAU - Zhang, Haitong AU - Zhang H AD - Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, People's Republic of China. FAU - Zhang, Jinjin AU - Zhang J AD - Medical Research Center, Binzhou Medical University, Yantai, People's Republic of China. FAU - Ji, Yunxia AU - Ji Y AD - Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, People's Republic of China. FAU - Liu, Wenbo AU - Liu W AD - Medical Research Center, Binzhou Medical University, Yantai, People's Republic of China. FAU - Liu, Weili AU - Liu W AD - Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, People's Republic of China. FAU - Wang, Meirong AU - Wang M AD - Medical Research Center, Binzhou Medical University, Yantai, People's Republic of China. FAU - Lv, Changjun AU - Lv C AD - Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, People's Republic of China. FAU - Song, Xiaodong AU - Song X AD - Department of Cellular and Genetic Medicine, School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, People's Republic of China. FAU - Li, Hongbo AU - Li H AD - Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, People's Republic of China. FAU - Li, Minge AU - Li M AUID- ORCID: 0000-0002-8995-3443 AD - Department of Clinical Nursing, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Stem Cells JT - Stem cells (Dayton, Ohio) JID - 9304532 RN - EC 2.1.1.43 (EZH2 protein, human) RN - EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein) RN - 0 (STAT1 protein, human) RN - 0 (STAT1 Transcription Factor) RN - 0 (FOXK1 protein, human) RN - 0 (Forkhead Transcription Factors) SB - IM MH - Mice MH - Humans MH - Animals MH - *Pulmonary Fibrosis/therapy MH - Fibrosis MH - Lung/metabolism MH - *Mesenchymal Stem Cells/metabolism MH - Autophagy MH - Umbilical Cord MH - Enhancer of Zeste Homolog 2 Protein/genetics/metabolism MH - STAT1 Transcription Factor MH - Forkhead Transcription Factors/metabolism OTO - NOTNLM OT - HuR OT - autophagy OT - circRNA OT - human umbilical cord mesenchymal stem cells OT - pulmonary fibrosis EDAT- 2023/07/08 10:41 MHDA- 2023/10/09 06:42 CRDT- 2023/07/07 19:43 PHST- 2022/12/06 00:00 [received] PHST- 2023/06/13 00:00 [accepted] PHST- 2023/10/09 06:42 [medline] PHST- 2023/07/08 10:41 [pubmed] PHST- 2023/07/07 19:43 [entrez] AID - 7221330 [pii] AID - 10.1093/stmcls/sxad053 [doi] PST - ppublish SO - Stem Cells. 2023 Oct 8;41(10):928-943. doi: 10.1093/stmcls/sxad053.