Chong Huang1, Jin-Feng Zhan2, Yan-Xia Chen1, Cheng-Yun Xu1, Yan Chen3. 1. Department of Nephrology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, PR China. 2. Physical Examination Center of the Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, PR China. 3. Department of Nephrology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, PR China. Electronic address: chenyanabc@163.com.
Abstract
BACKGROUND: Vascular 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. METHODS: The 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. RESULTS: In 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. CONCLUSION: Our 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.
BACKGROUND:Vascular 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. METHODS: The 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. RESULTS: In 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. CONCLUSION: Our 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.