1. Negative feedback regulation between microRNA let-7g and LOX-1 mediated hypoxia-induced PASMCs proliferation.
- Author
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Zhang WF, Zhu TT, Xiong YW, Xiong AZ, Ge XY, Hu CP, and Zhang Z
- Subjects
- Animals, Cell Proliferation, Down-Regulation, Male, MicroRNAs genetics, Rats, Rats, Sprague-Dawley, Scavenger Receptors, Class E genetics, Feedback, Physiological, Hypoxia, MicroRNAs metabolism, Muscle, Smooth, Vascular cytology, Muscle, Smooth, Vascular metabolism, Pulmonary Artery cytology, Scavenger Receptors, Class E metabolism
- Abstract
Background: Pulmonary hypertension (PH) is a proliferative disorder associated with enhanced proliferation and suppressed apoptosis of pulmonary artery smooth muscle cells (PASMCs). Our lately study demonstrated that let-7g inhibited hypoxia-induced proliferation of PASMCs via repressing c-myc-Bmi-1-p16 signaling pathway. However, the upstream of let-7g has not yet been fully defined. Previous studies have shown that LOX-1, a target of let-7g, could also regulate the expression of let-7g in human aortic endothelial cells. In this present study, we aimed to investigate whether there is a negative feedback regulation between microRNA let-7g and LOX-1 in hypoxia-induced proliferation of PASMCs., Methods: SD Rats were exposed to hypoxia (10% O
2 , 3 weeks) to induce PH. HE staining was used to evaluate pulmonary artery remodeling. in situ hybridization and immunohistochemistry were performed to assess the expression and distribution of let-7g and LOX-1, respectively. MTS, EDU and flow cytometry were performed to evaluate PASMCs proliferation. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were conducted to assess the expression of let-7g, LOX-1, calpain-1,-2,-4, and OCT-1., Results: The expression of let-7g was significantly down-regulated in pulmonary arteries of hypoxia-induced PH rats accompanied by pulmonary vascular remodeling, whereas let-7g mimic inhibited hypoxia-induced proliferation of PASMCs and up-regulation of LOX-1 expression. LOX-1 blocking reversed hypoxia-induced down-regulation of let-7g expression. Calpains, protein kinase C and OCT-1 were involved in negative feedback regulation between let-7g and LOX-1., Conclusion: Negative feedback regulation between let-7g and LOX-1 mediated hypoxia-induced proliferation of in PASMCs., (Copyright © 2017 Elsevier Inc. All rights reserved.)- Published
- 2017
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