Zhao Hong, Dong Yanting, Tian Xinrui, Tan Thian Kui, Liu Zhuola, Zhao Ye, Zhang Yun, Harris David Ch, Zheng Guoping
Hong Zhao, Yanting Dong, Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, Shaanxi Province, China.
World J Nephrol. 2013 Aug 6;2(3):84-9. doi: 10.5527/wjn.v2.i3.84.
Matrix metalloproteinases (MMPs) are members of the neutral proteinase family. They were previously thought to be anti-fibrotic because of their ability to degrade and remodel of extracellular matrix. However, recent studies have shown that MMPs are implicated in initiation and progression of kidney fibrosis through tubular cell epithelial-mesenchymal transition (EMT) as well as activation of resident fibroblasts, endothelial-mesenchymal transition (EndoMT) and pericyte-myofibroblast transdifferentiation. Interstitial macrophage infiltration has also been shown to correlate with the severity of kidney fibrosis in various chronic kidney diseases. MMPs secreted by macrophages, especially MMP-9, has been shown by us to be profibrotic by induction of tubular cells EMT. EMT is mainly induced by transforming growth factor-β (TGF-β). However, MMP-9 was found by us and others to be up-regulated by TGF-β1 in kidney tubular epithelial cells and secreted by activated macrophages, resulting in EMT and ultimately kidney fibrosis. Therefore, MMP-9 may serve as a potential therapeutic target to prevent kidney fibrosis in chronic kidney disease. This review, by a particular focus on EMT, seeks to provide a comprehensive understanding of MMPs, especially MMP-9, in kidney fibrosis.
基质金属蛋白酶（MMPs）是中性蛋白酶家族的成员。它们曾因具有降解和重塑细胞外基质的能力而被认为具有抗纤维化作用。然而，最近的研究表明，MMPs通过肾小管上皮细胞-间充质转化（EMT）以及驻留成纤维细胞的激活、内皮-间充质转化（EndoMT）和周细胞-肌成纤维细胞转分化参与肾纤维化的起始和进展。在各种慢性肾脏病中，肾间质巨噬细胞浸润也与肾纤维化的严重程度相关。我们的研究表明，巨噬细胞分泌的MMPs，尤其是MMP-9，可通过诱导肾小管上皮细胞EMT发挥促纤维化作用。EMT主要由转化生长因子-β（TGF-β）诱导。然而，我们和其他人发现，MMP-9在肾小管上皮细胞中被TGF-β1上调，并由活化的巨噬细胞分泌，导致EMT并最终引发肾纤维化。因此，MMP-9可能是预防慢性肾脏病肾纤维化的潜在治疗靶点。本综述特别关注EMT，旨在全面了解MMPs，尤其是MMP-9在肾纤维化中的作用。
