MicroRNA-21-5p regulates autophagy and apoptosis via the activation of the PI3K/AKT/mTOR signaling pathway and reducing H2O2-induced damage in primary AEC-II.
Xinxin Liu, Qiuyu Dai, Jie Zheng, Song Qin, Yingcong Ren, Kun Yu, Banghai Feng, Miao Chen, Hong Mei
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引用次数: 0
Abstract
Objective: We examined whether miR-21-5p activates the PI3K/AKT/mTOR signaling pathway, thereby inhibiting autophagy and apoptosis induced by H2O2 in AEC II cells.
Introduction: MicroRNA and autophagy play crucial roles in important biological processes during hyperoxia-induced acute lung injury. Located on chromosome 17q23.1, miR-21-5p, as a critical component of the miRNAs family, significantly contributes to the regulation of cell growth, apoptosis, and autophagy. However, the underlying mechanism through which miR-21-5p suppresses H2O2-induced autophagy and apoptosis of primary AEC-II in vitro remains to be fully elucidated.
Methods: To investigate the regulatory role of miR-21-5p in autophagy, primary type II alveolar epithelial cells (AEC-II) were isolated from rat lung tissue and subjected to 0.5 mmol/L H2O2 in a cell culture environment to simulate hyperoxia-induced acute lung injury. Cell viability was detected by cell counting Kit 8. Reactive oxygen species and apoptosis were detected by flow cytometry. Autophagy levels in AEC-II were evaluated by autophagic double marker method. The expressions of apoptosis and autophagy related proteins were detected by Western blotting.
Results: We found that in the process of H2O2 injury of AEC-II, the level of autophagy flow was up-regulated and the expression of miR-21-5p was down-regulated. Overexpression of miR-21-5p can significantly reduce the level of autophagy flow, inhibit apoptosis, and activate the AKT/mTOR signaling pathway.We pretreated with rapamycin, an mTOR inhibitor, to block the biological effects of miR-21-5p. In addition, pretreatment with MHY1485, an mTOR activator, inhibited AEC-II autophagy flow levels and increased apoptosis.
Conclusion: In summary, miR-21-5p can inhibit H2O2-induced AEC-II apoptosis and autophagy flow, which is partially mediated by the AKT/mTOR signaling pathway.MiR-21-5p could be used as both a clinical biomarker and a promising molecular target in patients with HALI.
期刊介绍：
International Journal of Immunopathology and Pharmacology is an Open Access peer-reviewed journal publishing original papers describing research in the fields of immunology, pathology and pharmacology. The intention is that the journal should reflect both the experimental and clinical aspects of immunology as well as advances in the understanding of the pathology and pharmacology of the immune system.
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