基础医学与临床2026，Vol.46Issue(5)：673-680,8.DOI:10.16352/j.issn.1001-6325.2026.05.0673
脂联素/APPL1轴调控紧密连接减轻糖尿病血管内皮细胞损伤
Adiponectin/APPL1 axis alleviates diabetic vascular endothelial injury by regulating tight junctions
摘要
Abstract
Objective To investigate the downstream molecular mechanisms by which the adiponectin(APN)/APPL1 signaling axis alleviates diabetic vascular endothelial injury.Methods APPL1-knockout diabetic mice were treated with APN.Hindlimb ischemia models were established to evaluate vascular regeneration.Endothelial injury and apoptosis were assessed by Western blot and caspase-3 activity.Human umbilical vein endothelial cells(HU-VECs)were transfected with APPL1 siRNA to examine the effects of APN on apoptosis and permeability.Tran-scriptomic profiling was performed followed by GO and KEGG enrichment analyses.Selected targets were validated by RT-qPCR.Results APN markedly improved hindlimb blood flow recovery,increased CD31 expression and suppressed caspase-3 activity in diabetic mice,whereas these protective effects were completely abrogated in the absence of APPL1(P＜0.01).Consistently,in HUVECs,APN reduced high glucose/high lipid-induced apoptosis and permeability,but APPL1 silencing abolished these injury-suppressive effects(P＜0.01).Transcriptomic analysis identified 1 559 genes regulated by the APN/APPL1 signaling axis,predominantly enriched in tight junc-tions,cell adhesion and Hippo signaling pathways.Validation studies highlighted Occludin,a central tight junction protein,whose expression was strictly dependent on APPL1.Conclusions APN alleviates diabetic vascular endo-thelial injury through an APPL1-dependent signaling mechanism,with Occludin emerging as a pivotal downstream molecular target.关键词
脂联素(APN)/APPL1/糖尿病/血管内皮/紧密连接Key words
adiponectin(APN)/APPL1/diabetes/vascular endothelium/tight junction分类
医药卫生引用本文复制引用
段艳茹,阮燕萍,陈洁,邢媛媛..脂联素/APPL1轴调控紧密连接减轻糖尿病血管内皮细胞损伤[J].基础医学与临床,2026,46(5):673-680,8.基金项目
北京市自然科学基金(7232011) （7232011）
