RGD Reference Report - Negative feedback regulation between microRNA let-7g and LOX-1 mediated hypoxia-induced PASMCs proliferation. - Rat Genome Database

RGD Reference Report - Negative feedback regulation between microRNA let-7g and LOX-1 mediated hypoxia-induced PASMCs proliferation. - Rat Genome Database

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Negative feedback regulation between microRNA let-7g and LOX-1 mediated hypoxia-induced PASMCs proliferation.
Authors:	Zhang, Wei-Fang Zhu, Tian-Tian Xiong, You-Wen Xiong, Ai-Zhen Ge, Xiao-Yue Hu, Chang-Ping Zhang, Zheng
Citation:	Zhang WF, etal., Biochem Biophys Res Commun. 2017 Jul 8;488(4):655-663. doi: 10.1016/j.bbrc.2017.01.073. Epub 2017 Jan 18.
RGD ID:	13464258
Pubmed:	PMID:28108289 (View Abstract at PubMed)
DOI:	DOI:10.1016/j.bbrc.2017.01.073 (Journal Full-text)
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.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
negative regulation of gene expression	involved_in	IMP		13464258; 13464258	PMID:28108289	BHF-UCL

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Genes (Rattus norvegicus)

Olr1 (oxidized low density lipoprotein receptor 1)

Pou2f1 (POU class 2 homeobox 1)

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