Negative feedback regulation between microRNA let-7g and LOX-1 mediated hypoxia-induced PASMCs proliferation
| Autor: | Xiao-Yue Ge, Wei-Fang Zhang, Chang-Ping Hu, You-Wen Xiong, Tian-Tian Zhu, Ai-Zhen Xiong, Zheng Zhang |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Biophysics Down-Regulation In situ hybridization Pulmonary Artery Biology Biochemistry Muscle Smooth Vascular Rats Sprague-Dawley 03 medical and health sciences microRNA medicine Animals Hypoxia Molecular Biology Protein kinase C Cell Proliferation Feedback Physiological Cell Biology Hypoxia (medical) Scavenger Receptors Class E medicine.disease Pulmonary hypertension Molecular biology Rats Cell biology Blot MicroRNAs 030104 developmental biology Apoptosis medicine.symptom Signal transduction |
| Zdroj: | Biochemical and Biophysical Research Communications. 488:655-663 |
| ISSN: | 0006-291X |
| Popis: | 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% O2, 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. |
| Databáze: | OpenAIRE |
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