Choe Nakwon, Shin Sera, Kim Young-Kook, Kook Hyun, Kwon Duk-Hwa
Department of Pharmacology, Chonnam National University Medical School, Hwasun 58128, Republic of Korea.
Basic Research Laboratory for Vascular Remodeling, Chonnam National University Medical School, Hwasun 58128, Republic of Korea.
Int J Mol Sci. 2024 Dec 20;25(24):13667. doi: 10.3390/ijms252413667.
Calcium deposition in vascular smooth muscle cells (VSMCs), a form of ectopic ossification in blood vessels, can result in rigidity of the vasculature and an increase in cardiac events. Here, we report that CCAAT/enhancer-binding protein beta (C/EBPβ) potentiates calcium deposition in VSMCs and mouse aorta induced by inorganic phosphate (Pi) or vitamin D. Based on cDNA microarray and RNA sequencing data of Pi-treated rat VSMCs, C/EBPβ was found to be upregulated and thus selected for further evaluation. Quantitative RT-PCR and Western blot analysis confirmed that C/EBPβ was upregulated in Pi-treated A10 cells, a rat VSMC line, as well as vitamin D-treated mouse aorta. The overexpression of C/EBPβ in A10 cells increased bone runt-related transcription factor 2 (), alkaline phosphatase (), and osteopontin () mRNA in the presence of Pi, as well as potentiating the Pi-induced increase in calcium contents. The Runx2 expression was increased by C/EBPβ through Runx2 P2 promotor. Our results suggest that a Pi-induced increase in C/EBPβ is a critical step in vascular calcification.
血管平滑肌细胞（VSMC）中的钙沉积是血管异位骨化的一种形式，可导致血管僵硬并增加心脏事件的发生。在此，我们报告CCAAT/增强子结合蛋白β（C/EBPβ）增强了无机磷酸盐（Pi）或维生素D诱导的VSMC和小鼠主动脉中的钙沉积。基于Pi处理的大鼠VSMC的cDNA微阵列和RNA测序数据，发现C/EBPβ上调，因此选择其进行进一步评估。定量RT-PCR和蛋白质印迹分析证实，在Pi处理的大鼠VSMC系A10细胞以及维生素D处理的小鼠主动脉中，C/EBPβ上调。在存在Pi的情况下，A10细胞中C/EBPβ的过表达增加了 runt相关转录因子2（Runx2）、碱性磷酸酶（ALP）和骨桥蛋白（OPN）的mRNA水平，同时增强了Pi诱导的钙含量增加。C/EBPβ通过Runx2 P2启动子增加了Runx2的表达。我们的结果表明，Pi诱导的C/EBPβ增加是血管钙化的关键步骤。
