Huang Yongpan, Zhan Wei, Song Chong, Tan Meihua, Wu Li, Wu Sina
School of Medicine, Changsha Social Work College, Changsha, Hunan, China.
Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China.
PLoS One. 2025 May 12;20(5):e0323058. doi: 10.1371/journal.pone.0323058. eCollection 2025.
Accumulation of calcium phosphate crystals is associated with vascular calcification (VC); however, the mechanism that promotes VC remains unclear. Accumulating evidence indicates that smooth muscle and endothelial cell-enriched migration/differentiation-associated lncRNA (SENCR) exerts a critical role in VC. This work focuses on the molecules involved in β-glycerophosphate-induced osteogenic differentiation of vascular smooth muscle cells (VSMCs) through SENCR epigenetic modification of Runx2 in an endoplasmic reticulum stress (ERS)-dependent manner.
We cultured VSMCs to explore the relationship among β-glycerophosphate, SENCR, and VC and also investigate the function of SENCR in β-glycerophosphate-induced osteogenic differentiation and VC in vitro.
Our findings indicate that β-glycerophosphate enhanced SENCR, MSH homeobox 2, Runx2, ERS-related markers, alkaline phosphatase activity, and cellular calcium deposition and suppressed the expression of α-SMA, SM 22α, and miR-4731-5p. SENCR silencing increased miR-4731-5p expression, which subsequently inhibited β-glycerophosphate-associated endoplasmic reticulum stress at the post-transcriptional level. Critically, the facts that direct interplay between SENCR and miR-4731-5p, and the downregulation of miR-4731-5p efficiently reversed the suppression of ERS-induced by SENCR silencing were observed. Collectively, the present study clarifies a novel mechanism by which downregulation of SRNRC contributes to the ERS-dependent osteogenic differentiation of VSMCs and VC by sponging miR-4731-5p. This study demonstrates that SENCR/miR-4731-5p axis is involved in β-glycerophosphate-mediated VC in vitro.
磷酸钙晶体的积累与血管钙化（VC）相关；然而，促进VC的机制仍不清楚。越来越多的证据表明，富含平滑肌和内皮细胞的迁移/分化相关长链非编码RNA（SENCR）在VC中发挥关键作用。本研究聚焦于通过内质网应激（ERS）依赖的方式，经SENCR对Runx2进行表观遗传修饰，参与β-甘油磷酸诱导血管平滑肌细胞（VSMC）成骨分化的分子。
我们培养VSMC以探究β-甘油磷酸、SENCR和VC之间的关系，并在体外研究SENCR在β-甘油磷酸诱导的成骨分化和VC中的作用。
我们的研究结果表明，β-甘油磷酸增强了SENCR、MSH同源盒2、Runx2、ERS相关标志物、碱性磷酸酶活性和细胞钙沉积，并抑制了α-SMA、SM 22α和miR-4731-5p的表达。SENCR沉默增加了miR-4731-5p的表达，随后在转录后水平抑制了β-甘油磷酸相关的内质网应激。至关重要的是，观察到SENCR与miR-4731-5p之间存在直接相互作用，并且miR-4731-5p的下调有效逆转了SENCR沉默诱导的ERS抑制。总的来说，本研究阐明了一种新机制，即SRNRC的下调通过海绵化miR-4731-5p促进VSMC的ERS依赖性成骨分化和VC。本研究表明SENCR/miR-4731-5p轴参与体外β-甘油磷酸介导的VC。
