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The lncRNA TUG1/miR-145-5p/FGF10 regulates proliferation and migration in VSMCs of hypertension.
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The lncRNA TUG1/miR-145-5p/FGF10 regulates proliferation and migration in VSMCs of hypertension.

Biochem Biophys Res Commun. 2018 May 11;:

Authors: Shi L, Tian C, Sun L, Cao F, Meng Z

Abstract
Vascular remodeling is a characteristic pathological feature of hypertension, it can cause of increasing vascular resistance and decrease of compliance. Vascular smooth muscle cell (VSMCs) dysfunction is the important foundation of vascular remodeling. Increasing evidences have revealed that lncRNA is an important regulatory factor of VSMC function. In this paper, we explored the function of lncRNA TUG1 in vascular remodeling of hypertension. Here, we found that lncRNA TUG1 was highly expressed in aorta of spontaneously hypertensive rats (SHR) rats and promoted the proliferation and migration of VSMCs (SHR-VSMCs). Bioinformatics analyze showed that lncRNA TUG1 sequence had miR-145-5p binding sites. Luciferase reporter test, RNA pulldown and qRT-PCR showed that lncRNA TUG1 could bind miR-145-5p. Similarly, bioinformatics analyze found that FGF10 3 'UTR contained miR-145-5p binding sites. Luciferase reporter test, qRT-PCR and Western blot were shown that miR-145-5p inhibited FGF10 expression by binding to its 3 'UTR. MTT showed that miR-145-5p inhibited and FGF10 promoted SHR-VMSCs proliferation and migration. Overexpression of miR-145-5p or knocking down of FGF10 after overexpresion of lncRNA TUG1 could rescue the proliferation and migration promoted by lncRNA TUG1. LncRNA TUG1 and FGF10 promoted and miR-145-5p suppressed the expression of β-catenin, TCF and LEF in SHR-VSMCs. Therefore, lncRNA TUG1/miR-145-5p/FGF10 promotes the proliferation and migration of VSMCs in hypertensive state by activating the Wnt/β-catenin pathway.

PMID: 29758198 [PubMed - as supplied by publisher]

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