Key result
miR-93-5p and miR-374a-5p overexpression suppresses calcification in human aortic valve cells.
Why the study?
The regulatory functions of microRNAs in the osteogenic differentiation of human aortic valvular interstitial cells in patients with chronic kidney disease remain largely unknown.
Does overexpression of miR-93-5p and miR-374a-5p suppress osteogenic differentiation in human aortic valvular interstitial cells?
Does overexpression of miR-93-5p and miR-374a-5p suppress osteogenic differentiation in human aortic valvular interstitial cells?
Overexpression of miR-93-5p and miR-374a-5p suppresses osteogenic differentiation of human aortic valvular interstitial cells via the BMP2/Smad1/5/Runx2 pathway, offering potential therapeutic targets for aortic valve calcification.
May support miR-93-5p/miR-374a-5p as targets in valvular calcification; hypothesis-generating pending in vivo validation.
Aortic valve calcification commonly occurs in patients with chronic kidney disease (CKD). However, the regulatory functions of microRNAs (miRNAs/miRs) in the osteogenic differentiation of human aortic valvular interstitial cells (hAVICs) in patients with CKD remain largely unknown. This study aimed to explore the functional role and underlying mechanisms of miR-93-5p and miR-374a-5p in the osteogenic differentiation of hAVICs. For this purpose, hAVICs calcification was induced with high-calcium/high-phosphate medium and the expression levels of miR-93-5p and miR-374a-5p were determined using bioinformatics assay. Alizarin red staining, intracellular calcium content, and alkaline phosphatase activity were used to evaluate calcification. The expression levels of bone morphogenetic protein-2 (BMP2), runt-related transcription factor 2 (Runx2), and phosphorylated (p)-Smad1/5 were detected by luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blot analysis. The results revealed that the expression levels of miR-93-5p and miR-374a-5p were significantly decreased in hAVICs in response to high-calcium/high-phosphate medium. The overexpression of miR-93-5p and miR-374a-5p effectively suppressed the high-calcium/high-phosphate-induced calcification and osteogenic differentiation makers. Mechanistically, the overexpression of miR-93-5p and miR-374a-5p inhibits osteogenic differentiation by regulating the BMP2/Smad1/5/Runx2 signaling pathway. Taken together, this study indicates that miR-93-5p and miR-374a-5p suppress the osteogenic differentiation of hAVICs associated with calcium-phosphate metabolic dyshomeostasis through the inhibition of the BMP2/Smad1/5/Runx2 signaling pathway.
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Liu et al. (2023) studied Aortic valve calcification. Overexpression of miR-93-5p and miR-374a-5p vs. High-calcium/high-phosphate medium without overexpression was evaluated on Osteogenic differentiation and mineralization. Overexpression of miR-93-5p and miR-374a-5p suppressed high-calcium/high-phosphate-induced calcification and osteogenic differentiation of human aortic valvular interstitial cells.
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