Publication: MicroRNA-141-3p mediates epithelial cell proliferation, apoptosis, and epithelial-mesenchymal transition and alleviates pulmonary fibrosis in mice via Spred2
Authors
Zhu, Liang ; Chen, Mo ; Wang, Wenwen ; Zhu, Jianing ; Wu, Huaxiang
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Publisher
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DOI
https://doi.org/10.14670/HH-18-585
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info:eu-repo/semantics/article
Description
Abstract
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 dualluciferase 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 αSMA and COl 1 expression while enhancing proliferation in TGF-β1-treated MLE-12 cells. Mechanistically, Spred2 was a target gene of miR-1413p. 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 epithelialmesenchymal transition and apoptosis of epithelial cells, as well as ameliorating PF in mice
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Citation
Histology and Histopathology Vol. 38, nº11 (2023)
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