Department of Intensive Care Unit, The First People's Hospital of Ziyang, Ziyang, 641300, China.
Department of Orthopedics, Kunming Medical University Second Affiliated Hospital, Kunming, 650033, China.
Curr Med Sci. 2024 Apr;44(2):369-379. doi: 10.1007/s11596-024-2862-6. Epub 2024 Apr 15.
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.
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.
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.
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.
基质金属蛋白酶 13（MMP13）是一种细胞外基质蛋白酶，通过降解胶原、修饰蛋白结构和调节炎症反应来影响动脉粥样硬化斑块和动脉血栓的进展，但它在深静脉血栓形成（DVT）中的作用尚未确定。本研究旨在探讨 MMP13 及其相关基因对 DVT 形成的潜在影响。
我们在体内改变 MMP13 的表达水平，并进行转录组研究，以检查 MMP13 及其相关基因在 DVT 小鼠模型中的表达和关系。在筛选出与 DVT 小鼠中 MMP13 相关的候选基因后，评估了候选基因在人脐静脉内皮细胞（HUVECs）和静脉壁中的表达水平。在体外研究了 MMP13 对 HUVECs 血小板聚集的影响。
在差异表达基因中，选择白细胞介素 1β、足突蛋白（Pdpn）和因子 VIII 血管性血友病因子（F8VWF）在小鼠中进行分析。当抑制 MMP13 时，Pdpn 的表达水平在体外显著下降。在 HUVECs 中，过表达 MMP13 导致 Pdpn 的表达水平增加，并诱导血小板聚集，而 Pdpn-siRNA 的转染削弱了 MMP13 增加血小板聚集的能力。
抑制 MMP13 的表达可以减轻小鼠 DVT 的负担。其机制涉及通过 MMP13 下调 Pdpn 的表达，这为 DVT 的诊断和治疗提供了一个新的基因靶点。
