MicroRNA-141-3p mediates epithelial cell proliferation, apoptosis, and epithelial-mesenchymal transition and alleviates pulmonary fibrosis in mice via Spred2
Liang Zhu1, Mo Chen1, Wenwen Wang1, Jianing Zhu2 and Huaxiang Wu1
1Department of Rheumatology and 2Department of Ultrasonic, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China
Corresponding Author: Huaxiang Wu, Department of Rheumatology, The Second Affiliated Hospital Zhejiang University School of Medicine, No.88, Jiefang Rd, Shangcheng District, Hangzhou, Zhejiang 310009, PR China. e-mail: wuhx8855@zju.edu.cn
Summary. Objective. This study probed the mechanism of microRNA (miR)-141-3p in the progression of pulmonary fibrosis (PF).
Methods. Mice were intratracheally administered with bleomycin (BLM) to establish a PF mouse model. To investigate the effects of miR-141-3p/Spred2 on PF in mice, PF mice received tail vein injections with agomir-141-3p and/or adenovirus vectors overexpressing Spred2 one week after BLM treatment. Then, the pathological changes of lung tissues were analyzed with H&E and Masson’s trichrome staining, and hydroxyproline contents in lung tissues were measured. For cell experiments, after loss- and gain-of-function assays, the role of miR-141-3p/Spred2 in the apoptosis and viability of TGF-β1-stimulated MLE-12 cells was examined by flow cytometry and CCK-8 assay, respectively. miR-141-3p, Spred2, COl 1, and α-SMA expression was determined in cells and mice. Then, the binding of miR-141-3p to Spred2 was tested with a dual-luciferase reporter assay.
Results. There were abnormally upregulated Spred2 and downregulated miR-141-3p in lung tissues of PF mice. TGF-β1 decelerated viability and augmented apoptosis and COl 1 and α-SMA expression in MLE-12 cells. Spred2 knockdown diminished apoptosis and α-SMA and COl 1 expression while enhancing proliferation in TGF-β1-treated MLE-12 cells. Mechanistically, Spred2 was a target gene of miR-141-3p. miR-141-3p upregulation accelerated proliferation and repressed apoptosis and α-SMA and COl 1 expression in TGF-β1-treated MLE-12 cells, which was nullified by further overexpressing Spred2. miR-141-3p alleviated PF in mice by targeting Spred2.
Conclusion. miR-141-3p negatively modulates Spred2 to promote proliferation and repress epithelial-mesenchymal transition and apoptosis of epithelial cells, as well as ameliorating PF in mice. Histol Histopathol 38, 1269-1282 (2023)
Key words: microRNA-141-3p, Spred2, Lung epithelial cells, Proliferation, Apoptosis, Pulmonary fibrosis
DOI: 10.14670/HH-18-585
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©The Author(s) 2023. Open Access. This article is licensed under a Creative Commons CC-BY International License. |
