Matrix Metalloproteinases in Kidney Disease: Role in Pathogenesis and Potential as a Therapeutic Target

Abstract

Matrix metalloproteinases (MMPs) are large family of proteinases. In addition to a fundamental role in the remodeling of the extracellular matrix, they also cleave a number of cell surface proteins and are involved in multiple cellular processes. MMP activity is regulated via numerous mechanisms, including inhibition by endogenous tissue inhibitors of metalloproteinases (TIMPs). Similar to MMPs, a role for TIMPs has been established in multiple cell signaling pathways. Aberrant expression of MMPs and TIMPS in renal pathophysiology has long been recognized, and with the generation of specific knockout mice, the mechanistic role of several MMPs and TIMPs is becoming more understood and has revealed both pathogenic and protective roles. This chapter will focus on the expression and localization of MMPs and TIMPs in the kidney, as well as summarizing the current information linking these proteins to acute kidney injury and chronic kidney disease. In addition, we will summarize studies suggesting that MMPs and TIMPs may be biomarkers of renal dysfunction and represent novel therapeutic targets to attenuate kidney disease.

Keywords: Acute kidney injury; Chronic allograft nephropathy; Chronic kidney disease; Diabetic nephropathy; Glomerulosclerosis; Matrix metalloproteinases; Polycystic kidney disease; Tissue inhibitor of metalloproteinase; Tubulointerstitial fibrosis.