山西医科大学学报2026，Vol.57Issue(8)：904-914,11.DOI:10.13753/j.issn.1007-6611.2026.08.007
Sema4D在川崎病血管内皮间质转化中的作用及机制
Role and mechanism of Sema4D in endothelial-to-mesenchymal transition in Kawasaki disease
摘要
Abstract
Objective To investigate the role of Sema4D in endothelial-to-mesenchymal transition(EndMT)in Kawasaki disease(KD)and its underlying molecular mechanisms.Methods To observe the effect of Sema4D on EndMT,human coronary artery endo-thelial cells(HCAECs)were divided into HC group,KD group and KD+VX15/2503 group.The HC group was treated with 20%pooled serum from healthy children,the KD group was treated with 20%pooled serum from children with KD,and the KD+VX15/2503 group was treated with 20%pooled KD serum after pre-treatment with the Sema4D neutralizing antibody VX15/2503.RT-qPCR was performed to detect the mRNA expressions of endothelial markers(CD31,VE-cadherin,ZO-1)and mesenchymal markers(α-SMA,Vimentin)related to EndMT in cells.To investigate the role of PlexinB receptors in Sema4D-induced EndMT,HCAECs were divided into KD group,KD+si-ctrl group,KD+si-PlexinB1 group and KD+si-PlexinB2 group,and RT-qPCR was used to measure the mRNA expressions of EndMT markers.To analyze the regulatory effect of Sema4D on the NLRP3 inflammasome and NF-κB signaling,HCAECs were also divided into KD group,rhSema4D group,rhSema4D+si-ctrl group,rhSema4D+si-PlexinB1 group and rhSema4D+si-PlexinB2 group;RT-qPCR was used to detect the mRNA expressions of NLRP3 inflammasome-related genes(NLRP3,ASC,cas-pase-1,IL-1β and IL-18),and Western blot was used to assess NF-κB p65 phosphorylation(p-p65)level.To explore whether NLRP3 participates in Sema4D-mediated EndMT,HCAECs were divided into KD+si-ctrl group,KD+si-NLRP3 group,rhSema4D+si-ctrl group and rhSema4D+si-NLRP3 group;RT-qPCR was carried out to quantify the mRNA expressions of EndMT markers.To verify that NF-κB triggers EndMT by activating NLRP3,HCAECs were divided into two sets of groups:PBS group,BAY11-7082(inhibitor of NF-κB)group,PBS+rhSema4D group,BAY11-7082+rhSema4D group,and OE-ctrl+PBS group,OE-ctrl+rhSema4D group,OE-ctrl+BAY11-7082+rhSema4D group,OE-NLRP3+BAY11-7082+rhSema4D group;RT-qPCR was used to measure EndMT markers and NLRP3 expression.Results Compared with HC group,the KD group showed decreased expressions of endothelial markers(CD31,VE-cadherin and ZO-1)and increased expressions of mesenchymal markers(α-SMA and Vimentin,all P<0.05);these changes were reversed in KD+VX15/2503 group(P<0.05).Compared with KD+si-ctrl group,the KD+si-PlexinB2 group exhibited increased CD31,VE-cadherin and ZO-1 expressions,and decreased α-SMA and Vimentin expressions(all P<0.05),whereas no significant differences were observed in KD+si-PlexinB1 group.Compared with rhSema4D+si-ctrl group,the rhSema4D+si-PlexinB2 group showed reduced expressions of NLRP3 inflammasome-related genes and p-p65 level(P<0.05),while the rhSema4D+si-PlexinB1 group showed no sig-nificant differences.Compared with rhSema4D+si-ctrl group,the rhSema4D+si-NLRP3 group exhibited increased CD31,VE-cadherin and ZO-1 expressions,and decreased α-SMA and Vimentin expressions(P<0.05).Compared with PBS+rhSema4D group,the BAY11-7082+rhSema4D group showed increased expressions of CD31,VE-cadherin,and ZO-1,and decreased expressions of α-SMA,Vimentin and NLRP3(P<0.05).Compared with OE-ctrl+BAY11-7082+rhSema4D group,the OE-NLRP3+BAY11-7082+rh-Sema4D group exhibited decreased CD31,VE-cadherin and ZO-1 expressions,and increased α-SMA and vimentin expressions(P<0.05).Conclusion Sema4D induces EndMT in coronary artery endothelial cells by activating the NF-κB/NLRP3 signaling axis via its receptor PlexinB2.关键词
川崎病/血管内皮间质转化/信号素4D/神经丛素B2/核因子κB/NLRP3Key words
Kawasaki disease/endothelial-to-mesenchymal transition/semaphorin 4D/plexinB2/NF-κB/NLRP3分类
医药卫生引用本文复制引用
黄君华,张书婉..Sema4D在川崎病血管内皮间质转化中的作用及机制[J].山西医科大学学报,2026,57(8):904-914,11.基金项目
陕西省自然科学基础研究计划项目(2024JC-YBQN-0869) （2024JC-YBQN-0869）
西安市科技计划项目(24YXYJ0064) （24YXYJ0064）
西安市卫生健康委员会科研项目(2023qn12) （2023qn12）
