Vaspin alleviates the lncRNA LEF1-AS1-induced osteogenic differentiation of vascular smooth muscle cells via the Hippo/YAP signaling pathway

  • Exp Cell Res. 2022 Nov 2;421(2):113407. doi: 10.1016/j.yexcr.2022.113407.
Xiaoxue Ma  1 ,  Yiru Wang  1 ,  Qi Liu  1 ,  Baihe Han  1 ,  Gang Wang  1 ,  Ruoxi Zhang  2 ,  Xingtao Huang  1 ,  Xuedong Wang  1 ,  Mengyue Yang  1 ,  Chun Xing  1 ,  Jingbo Hou  3 ,  Bo Yu  1
Affiliations
  • 1. The Key Laboratory of Myocardial Ischemia Organization, Chinese Ministry of Education, Harbin, China; Department of Cardiology Organization, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • 2. Department of Cardiology, Harbin Yinghua Hospital, Harbin, China.
  • 3. The Key Laboratory of Myocardial Ischemia Organization, Chinese Ministry of Education, Harbin, China; Department of Cardiology Organization, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: [email protected].
PMID: 36334793 DOI: 10.1016/j.yexcr.2022.113407
Abstract

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 osteogenic 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 α-smooth muscle actin (α-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.

Keywords
Osteogenic differentiation; Vascular smooth muscle cell; Vaspin; YAP; lncRNA LEF1-AS1.
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