Inhibiting MMP13 Attenuates Deep Vein Thrombosis in a Mouse Model by Reducing the Expression of Pdpn  

作　　者：Ji LUO Jin ZHOU Jing-zeng LUO Hai-long WANG Xue-ling ZHAO Ru-dan ZHOU 

机构地区：[1]Department of Intensive Care Unit,The First People's Hospital of Ziyang,Ziyang 641300,China [2]Department of Orthopedics,Kunming Medical University Second Affiliated Hospital,Kunming 650033,China [3]Department of Orthopedics,Kunming Medical University First Affiliated Hospital,Kunming 650032,China [4]Department of Orthopedics,The Third People's Hospital of Yunnan Province,Kunming 650200,China

出　　处：《Current Medical Science》2024年第2期369-379,共11页当代医学科学（英文）

基　　金：supported by grants from General Project of Yunnan Basic Research Program(No.202301AT070104);the Joint Project of Kunming Medical University and Science and Technology Department of Yunnan Province(No.202001AY070001-185);the Joint Project of Kunming Medical University and Science and Technology Department of Yunnan Province(No.202101AY070001-119);Yunnan Provincial Orthopedic and Sports Rehabilitation Clinical Medicine Research Center(No.202102AA310068).

摘　　要：Objective:Matrix metalloproteinase 13(MMP13)is an extracellular matrix protease that affects the progression of atherosclerotic plaques and arterial thrombi by degrading collagens,modifying protein structures and regulating inflammatory responses,but its role in deep vein thrombosis(DVT)has not been determined.The purpose of this study was to investigate the potential effects of MMP13 and MMP13-related genes on the formation of DVT.Methods:We altered the expression level of MMP13 in vivo and conducted a transcriptome study to examine the expression and relationship between MMP13 and MMP13-related genes in a mouse model of DVT.After screening genes possibly related to MMP13 in DVT mice,the expression levels of candidate genes in human umbilical vein endothelial cells(HUVECs)and the venous wall were evaluated.The effect of MMP13 on platelet aggregation in HUVECs was investigated in vitro.Results:Among the differentially expressed genes,interleukin 1 beta,podoplanin(Pdpn),and factor VIII von Willebrand factor(F8VWF)were selected for analysis in mice.When MMP13 was inhibited,the expression level of PDPN decreased significantly in vitro.In HUVECs,overexpression of MMP13 led to an increase in the expression level of PDPN and induced platelet aggregation,while transfection of PDPN-siRNA weakened the ability of MMP13 to increase platelet aggregation.Conclusions:Inhibiting the expression of MMP13 could reduce the burden of DVT in mice.The mechanism involves downregulating the expression of Pdpn through MMP13,which could provide a novel gene target for DVT diagnosis and treatment.

关 键 词：deep vein thrombosis matrix metalloproteinase 13 PODOPLANIN 

分 类 号：R285.5[医药卫生—中药学]