中国药理学通报2024，Vol.40Issue(8)：1447-1454,8.DOI:10.12360/CPB202403084
Takeda G蛋白偶联受体5在血管平滑肌细胞增殖和迁移中的作用
Role of TGR5 in proliferation and migration of vascular smooth muscle cells
摘要
Abstract
Aim To explore the role of Takeda G pro-tein-coupled receptor 5(TGR5)in the proliferation and migration of vascular smooth muscle cells(VSMCs)within the intimal layer of mice.Methods Mouse VSMCs were stimulated for proliferation and migration with PDGF-BB,followed by administration of INT-777 for activation of TGR5.CCK-8 assay and Ki-67 immunofluorescence staining were employed to eval-uate cell proliferation.The scratch assay was utilized to assess migration.Western blot analysis was conducted to monitor TGR5 protein expression.To further investi-gate the role of TGR5 in intimal hyperplasia in vivo,20 male wild-type C57BL/6J mice were randomly divided into four groups:sham group,carotid artery endothelial injury group,sham+UDCA(ursodeoxy-cholic acid,a TGR5 agonist)group,and carotid artery endothelial injury+UDCA group(n=5 in each group).After the establishment of endothelial injury model,mice were orally fed with regular maintenance feed containing 0.5％UDCA for 21 days.Subsequent-ly,samples were collected for Hematoxylin and Eosin(HE)staining to assess the neointimal hyperplasia.Immunofluorescence(IF)staining was used to exam-ine the proliferation of VSMCs within the carotid inti-ma.Results The specific activation of TGR5 marked-ly diminished cell viability,the proportion of Ki-67-positive cells,and slowed down the rate of wound-heal-ing.Notably,the specific activation of TGR5 increases the expression of UCP2 in cells and reduces the levels of reactive oxygen species(ROS).The inhibitory effect of TGR5 on VSMC proliferation and migration was neutralized upon the restoration of intracellular ROS level with H2O2.Activation of TGR5 was found to mitigate intimal thickening following carotid artery inju-ry.Conclusion TGR5 may inhibit the proliferation and migration of mouse VSMCs by attenuating intracel-lular oxidative stress.关键词
细胞增殖/细胞迁移/血管平滑肌/再狭窄/G蛋白偶联胆汁酸受体1/INT-777Key words
cell proliferation/cell migration/vascular smooth muscle cells/intimal hyperplasia/G protein-coupled bile acid receptor 1/INT-777分类
医药卫生引用本文复制引用
杨曦,张黎,杨耀,王嘉,孙雄山,王强..Takeda G蛋白偶联受体5在血管平滑肌细胞增殖和迁移中的作用[J].中国药理学通报,2024,40(8):1447-1454,8.基金项目
四川省自然科学基金资助项目(No 2022NSFSC0820) （No 2022NSFSC0820）
国家自然科学基金资助项目(No 82100419) （No 82100419）
西部战区总医院院管课题(No 2024-YGJC-A06,2021-XZYG-B28) （No 2024-YGJC-A06,2021-XZYG-B28）
