Vaspin alleviates the lncRNA LEF1-AS1-induced osteogenic differentiation of vascular smooth muscle cells via the Hippo/YAP signaling pathway
Vaspin alleviates the lncRNA LEF1-AS1-induced osteogenic differentiation of vascular smooth muscle cells via the Hippo/YAP signaling pathway
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DOI：
10.1016/j.yexcr.2022.113407
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发表时间：
2022-11-04
影响因子：
3.7
通讯作者：
Yu, Bo
中科院分区：
文献类型：
--
作者：
Ma, Xiaoxue;Wang, Yiru;Yu, Bo
血管钙化（VC）与心血管疾病的高死亡率和高发病率密切相关，而血管平滑肌细胞（VSMC）向成骨样细胞的转化是VC发生的关键。LncRNA LEF 1-AS 1促进动脉粥样硬化和牙髓干细胞钙化，而其在VC中的作用尚不清楚。内脏脂肪组织来源的丝氨酸蛋白酶抑制剂（vaspin）是一种调节骨代谢的脂肪因子。然而，vaspin和VC之间的关系仍然不清楚。本研究旨在探讨LEF 1-AS 1在VSMC成骨转化中的作用，以及vaspin是否抑制LEF 1-AS 1介导的VSMC成骨分化，并探讨其可能机制。在这项研究中，定量实时聚合酶链反应（qRT-PCR）和蛋白质印迹分析表明，LEF 1-AS 1过表达显著上调成骨标志物Runt相关转录因子-2（RUNX 2）水平，下调VSMC收缩标志物α-平滑肌肌动蛋白（α-SMA）水平。茜素红染色、碱性磷酸酶（ALP）染色、ALP活性测定和钙含量测定也表明LEF 1-AS 1过表达促进VSMCs钙沉积。然而，vaspin治疗消除了这种现象。在机制上，LEF 1-AS 1显著降低磷酸化雅普水平，而vaspin逆转LEF 1-AS 1诱导的磷酸化雅普下降。结果表明，LEF 1-AS 1通过调控Hippo/雅普通路促进VSMCs的成骨分化，而vaspin则消除了LEF 1-AS 1介导的VSMCs成骨表型转换。
Vascular calcification (VC) is closely related to higher cardiovascular mortality and morbidity, and vascular smooth muscle cell (VSMC) switching to osteogenic-like cells is crucial for VC. LncRNA LEF1-AS1 promotes atherosclerosis and dental pulp stem cells calcification, while its role in VC remains unknown. Visceral adipose tissue-derived serine protease inhibitor (vaspin) is an adipokine regulating bone metabolism. However, the relationship between vaspin and VC is still unclear. We aimed to explore the role of LEF1-AS1 on VSMC oste-ogenic transition, whether vaspin inhibited LEF1-AS1-mediated osteogenic differentiation of VSMCs, and the responsible mechanism. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis indicated that LEF1-AS1 overexpression significantly upregulated osteogenic marker Runt -related transcription factor-2 (RUNX2) level and downregulated VSMC contractile marker alpha-smooth muscle actin (alpha-SMA) level. Alizarin red staining, alkaline phosphatase (ALP) staining, ALP activity assay, and calcium content assay also suggested that LEF1-AS1 overexpression promoted calcium deposition in VSMCs. However, vaspin treatment abolished this phenomenon. Mechanistically, LEF1-AS1 markedly decreased phosphorylated YAP level, while vaspin reversed LEF1-AS1-induced phosphorylated YAP decline. Our results revealed that LEF1-AS1 accelerated the osteogenic differentiation of VSMCs by regulating the Hippo/YAP pathway, while vaspin eliminated the LEF1-AS1-meditated VSMCs osteogenic phenotype switch.