Affiliation:
1. Beijing Tsinghua Chang Gung Hospital
2. Chinese PLA General Hospital
3. Beijing Anzhen Hospital
Abstract
Abstract
LncRNA H19 was first discovered to be involved in vascular calcification (VC). Our previous research found that VC inhibits dual specific phosphatase 1 (DUSP1) and optic atrophy protein 1 (OPA1) proteins, increases calcium deposition, runt related transcription factor 2 (Runx-2), bone morphogenetic protein 2 (BMP-2) expression, and apoptosis. This study sought to explore whether H19 induces VC and promotes calcium deposition, osteogenic differentiation, and apoptosis through the DUSP1/OPA1 pathway. The cell and animal calcification model were used to explore the effects of H19 on DUSP1/OPA1 pathways. β-glycerophosphate was used to establish vascular smooth muscle cells (VSMCs) calcification model. ApoE −/− diabetes mice were fed with high-fat diet for 32 weeks to establish animal calcification model. Calcium deposition was detected by Alizarin Red S staining and von Kossa staining. To observe osteogenic differentiation, the expression of Runx-2 and BMP-2 were measured by Western blotting. And apoptosis was evaluated by TUNEL staining and cleaved caspase-3 detection. The expression of H19 significantly increased, while the expression of DUSP1 and OPA1 significantly decreased in VC. H19 knockdown could significantly increase the expression of DUSP1 and OPA1 proteins. When DUSP1 was deleted, OPA1 was decreased again (P < 0.001). H19 knockdown inhibits calcified nodules, and reduces calcium content, Runx-2, BMP-2, cleaved caspase-3 expression, and apoptosis rate (P < 0.001). The inhibition of DUSP1 or OPA1 under H19 knockdown promotes the formation of calcified nodules, and increases the calcium content, Runx-2, BMP-2, expression of cleaved caspase-3, and apoptosis rate (P < 0.001). H19 induces VC by inhibiting the DUSP1/OPA1 protein pathway, which may be related to the increasing calcium deposition, osteogenic differentiation, and apoptosis.
Publisher
Research Square Platform LLC
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