Negative feedback regulation between microRNA let-7g and LOX-1 mediated hypoxia-induced PASMCs proliferation

Journal Article · Sat Jul 08 04:00:00 EDT 2017 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2017.01.073· OSTI ID:22719013

Zhang, Wei-Fang ^[1]; Zhu, Tian-Tian ^[1]; Xiong, You-Wen ^[2]; Xiong, Ai-Zhen ^[3]; Ge, Xiao-Yue ^[1]; Hu, Chang-Ping ^[1]; Zhang, Zheng ^[1]

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1. Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078 (China)
2. Jiangxi Center of Medical Device Testing, Nanchang, 330029 (China)
3. Department of Pharmacy, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006 (China)

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{sub 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.

• OSTI ID: 22719013
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 488; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANOXIA
APOPTOSIS
ARTERIES
CELL PROLIFERATION
HYPERTENSION
IN-SITU HYBRIDIZATION
LET
PH VALUE
PHOSPHOTRANSFERASES
POLYMERASE CHAIN REACTION
POLYMERASES
RATS