LncRNA-SNHG29 inhibits vascular smooth muscle cell calcification by downregulating miR-200b-3p to activate the α-Klotho/FGFR1/FGF23 axis

Abstract

BackgroundVascular calcification (VC) is characterized by mineral accumulation on the walls of arteries and veins, which is a pathological process commonly found in elderly individuals and patients with atherosclerosis, hypertension, and diabetes. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play an important role in VC. However, the role of SNHG29 is less clear. MethodsThe expression of SNHG29, miR-200b-3p, α-Klotho, FGFR1 and FGF23 in vascular smooth muscle cells (VSMCs) was quantified by qRT-PCR and western blot assays. β-GP was used to construct an in vitro calcification model, followed by MTT assay to detect cell viability. Calcification was determined by alizarin red S staining and quantified by calcification assay. ALP activity was investigated by ALP staining. The interactions among SNHG29, miR-200b-3p and α-Klotho were verified by luciferase assay. ResultsIn the in vitro calcification model, SNHG29 was downregulated, while miR-200b-3p was upregulated. SNHG29 overexpression and miR-200b-3p knockdown significantly suppressed osteoblast-related factors (RUNX2 and BMP2), accompanied by activation of the α-Klotho/FGFR1/FGF23 axis, further inhibiting the formation of calcified nodules. Moreover, miR-200b-3p overexpression and α-Klotho knockdown reversed the SNHG29 overexpression-induced inhibitory effects on calcified VSMCs. ConclusionOur study is the first to demonstrate that SNHG29 could inhibit VSMC calcification by downregulating miR-200b-3p to activate the α-Klotho/FGFR1/FGF23 axis, suggesting SNHG29 as a novel therapeutic target for VC-associated diseases.