Matrix metalloproteinase 9 induces keratinocyte apoptosis through FasL/Fas pathway in diabetic wound
Matrix metalloproteinase 9 induces keratinocyte apoptosis through FasL/Fas pathway in diabetic wound
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基质金属蛋白酶9通过FasL/Fas途径诱导糖尿病伤口角质形成细胞凋亡
DOI：
10.1007/s10495-019-01536-w
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发表时间：
2019-08-01
期刊：
影响因子：
7.2
通讯作者：
Yan, Li
中科院分区：
文献类型：
--
作者：
Liang, Ying;Yang, Chuan;Yan, Li
细胞凋亡是去除组织中不需要的细胞的机制。在糖尿病伤口中，其特征在于延迟愈合过程，记录了过度的细胞凋亡并起着至关重要的作用。基质金属蛋白酶9（MMP 9）在糖尿病创面不愈合中升高，是创面愈合过程中必需的，但其异常导致创面愈合延迟。MMP 9的经典功能是降解细胞外基质（ECM）。然而，有一些文献证据表明，MMP 9触发细胞凋亡。过量的MMP 9是否参与了糖尿病延迟愈合创面表皮细胞凋亡及其机制尚不清楚。在这项研究中，我们的目的是探讨是否MMP9诱导角质形成细胞凋亡，并探讨可能的机制。我们的体外研究表明，晚期糖基化终末产物（AGEs）诱导角质形成细胞凋亡，并提高MMP 9水平。此外，MMP 9的细胞内表达和细胞外补充均促进细胞凋亡。此外，MMP 9导致FasL的表达增加，而不是Fas和p53。这些发现鉴定了MMP 9在延迟的糖尿病伤口愈合中发挥的新作用，这是由于对角质形成细胞的促凋亡作用，其由FasL表达的增加介导。这项研究增加了对参与糖尿病伤口修复的MMP9升高的理解，并为未来的新疗法提供了一些见解。
Apoptosis is a mechanism to remove unwanted cells in the tissue. In diabetic wound, which is characterized by delayed healing process, excessive apoptosis is documented and plays a crucial role. Matrix metalloproteinase 9 (MMP9), which is elevated in non-healed diabetic wound, is necessary for healing process but its abnormality resulted in a delayed healing. The classical function of MMP9 is the degradation of extracellular matrix (ECM). However, there is some literature evidence that MMP9 triggers cell apoptosis. Whether the excessive MMP9 contributes to epidermis cell apoptosis in delayed healing diabetic wound and the underlying mechanisms is not clear. In this study, we aimed to explore whether MMP9 induced keratinocyte apoptosis and investigate the plausible mechanisms. Our in vitro study showed that advanced glycation end products (AGEs) induced keratinocyte apoptosis and enhanced MMP9 level. Besides, MMP9, both intra-cellular expressions and extra-cellular supplement, promoted cell apoptosis. Further, MMP9 resulted in an increased expression of FasL, other than Fas and p53. These findings identified a novel effect that MMP9 exerted in delayed diabetic wound healing, owing to a pro-apoptotic effect on keratinocyte, which was mediated by an increase of FasL expression. This study increases understanding of elevated MMP9 which is involved in diabetic wound repair and offers some insights into novel future therapies.