Matrix Metalloproteinases and Their Inhibitors in Kidney Scarring: Culprits or Innocents

概要

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The renal extracellular matrix (ECM) is in a continual state of turnover with homeostasis maintained by balancing synthesis and degradation rates. During progressive kidney scarring an imbalance occurs leading to increase ECM either by increased deposition or decreased breakdown, although a combination of the two is more likely. Increased synthesis of many ECM proteins such as collagens I, III, and IV, fibronectin and laminin contribute to this imbalance; however decreased proteolytic activity leading to accumulation of ECM components is also an important component of scarring. The matrix metalloproteinases (MMPs) system is predominantly responsible for degrading mature ECM, consisting of 24 members, with MMPs 1, 2, 3, 8, 9, and 13 having significant renal expression. The kidney also expresses 3 Tissue inhibitors of MMPs; TIMP-1, 2, and 3. MMPs also have a role during kidney development. Several studies describe changes in ECM proteolysis and more specifically MMPs in end stage kidney disease (ESRD), although most of these are descriptive and based on enzymatic, protein or mRNA analysis of homogenates. There is no consistency in most of these studies regarding the expression of MMPs and TIMPS in experimental kidney scarring. Few of these studies have been investigated in human kidney scarring. Here is a comprehensive review of the MMPs and TIMPs literature including their action, activation, regulation, and contribution in experimental and human CKD.