4.4 Article

R-spondin 3 Inhibits High Glucose-Induced Endothelial Activation Through Leucine-Rich G Protein-Coupled Receptor 4/Wnt/β-catenin Pathway

期刊

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
卷 80, 期 1, 页码 70-81

出版社

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FJC.0000000000001295

关键词

R-spondin 3; endothelial activation; high glucose; LGR4/Wnt/beta-catenin

资金

  1. Ministry of Science and Technology of China [2021YFA0804803]
  2. National Natural Science Foundation of China [81930012, 81730013, 81720108003, 82130015]

向作者/读者索取更多资源

This article investigates the regulatory role of R-spondin 3 in high glucose-induced endothelial activation. It demonstrates that R-spondin 3 can inhibit endothelial activation and reveals the underlying mechanism involving the leucine-rich G protein-coupled receptor 4/Wnt/β-catenin pathway.
High glucose-induced endothelial activation plays critical roles in the development of diabetic vascular complications. R-spondin 3 could inhibit inflammatory damage, and diabetic vascular inflammation is secondary to endothelial activation. In this article, we identify R-spondin 3 as a novel regulator of high glucose-induced endothelial activation. We found that the serum levels of R-spondin 3 were significantly reduced in type 2 diabetic patients and db/db mice. We observed that the increased expressions of vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, and monocyte chemoattractant protein-1 (endothelial activation makers) in high glucose-stimulated human umbilical vein endothelial cell lines (HUVECs) could be inhibited by overexpressing R-spondin 3 or human R-spondin 3 recombinant protein. Subsequently, high glucose-induced adhesion and migration of human myeloid leukemia mononuclear cells (THP-1 cells) to HUVECs were markedly suppressed by the overexpression of R-spondin 3 in HUVECs. Moreover, the inhibitory effect of R-spondin 3 on the expressions of vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, and monocyte chemoattractant protein-1 in high glucose-treated HUVECs could be blocked by knockdown of leucine-rich G protein-coupled receptor 4 (R-spondin 3 receptor) or the specific inhibitor of Wnt/beta-catenin pathway. Taken together, R-spondin 3 could suppress high glucose-induced endothelial activation through leucine-rich G protein-coupled receptor 4/Wnt/beta-catenin pathway.

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