Matrix metalloproteinases (MMPs) are a large family of proteinases that remodel extracellular matrix (ECM) components and cleave a number of cell surface proteins. MMP activity is regulated via a number of mechanisms, including inhibition by tissue inhibitors of metalloproteinases (TIMPs). Originally thought to cleave only ECM proteins, MMP substrates are now known to include signaling molecules (growth factor receptors) and cell adhesion molecules. Recent data suggest a role for MMPs in a number of renal pathophysiologies, both acute and chronic. This review 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, glomerulosclerosis/tubulointerstitial fibrosis, chronic allograft nephropathy, diabetic nephropathy, polycystic kidney disease, and renal cell carcinoma.acute kidney injury; chronic allograft nephropathy; diabetic nephropathy; glomerulosclerosis; MMP; polycystic kidney disease; tissue inhibitor of metalloproteinase; tubulointerstitial fibrosis; renal cell carcinoma MATRIX METALLOPROTEINASES (MMPs) are zinc-containing endopeptidases that are involved in remodeling the extracellular matrix (ECM) and are crucial for tissue development and homeostasis. All MMPs are multidomain enzymes, generally consisting of a prodomain, a catalytic domain, a hinge region, and a hemopexin-like domain. Most MMPs are secreted as proMMPs; activation usually requires cleavage of the prodomain by plasmin or other MMPs (88). The propeptide sequence contains a conserved cysteine switch (PRCGXPD) to stabilize and inhibit the catalytic zinc ion, which is bound in a conserved HEXGHXXGXXH motif (53). The hemopexin-like domain is characterized by a "propeller" of four twisted ␤-sheets, which are thought to confer substrate recognition (53). Together, the hinge region and the hemopexin-like domain unravel substrate proteins for subsequent degradation. Originally thought to cleave only ECM proteins, this family of enzymes is now known to cleave a number of non-ECM substrates as well. For example, cell adhesion molecules (cadherins and integrins) and both growth factors and their receptors (TGF-␤, FGF-R1) are targeted by MMPs (74).Tissue inhibitors of metalloproteinases (TIMPs) are endogenous, specific inhibitors that bind and inhibit MMPs. Four TIMPs (TIMP-1-4) have been identified in vertebrates; these proteins share a similar structure which fits into the active site of the MMP catalytic domain. TIMPs inhibit all MMPs, except TIMP-1, which does not inhibit . A number of other MMP inhibitors have been identified, including RECK (81), ␣2-macroglobulin (4), and tissue factor pathway inhibitor-2 (33).MMPs are classified into six groups based on substrate and sequence homology: collagenases, gelatinases, stromelysins, matrilysins, membrane-type matrix metalloproteinases and "other MMPs" (Fig. 1). Collagenases [MMP-1, -8 (neutrophil collagenase), -13, and -18 (Xenopus laevis collagenase)] cleave collagens I, II, and III at a...

Taurine is a semiessential amino acid and naturally occurring antioxidant. One of its main roles is to protect tissues against attack by chlorinated oxidants particularly hypochlorous acid (HOCl). It is found in high concentrations in neutrophils and previous studies showed it possesses potent antimicrobial properties and attenuates high glucose induced endothelial cell apoptosis. In humans taurine has been shown to up‐regulate constitutive nitric oxide synthase (cNOS), a known cytoprotector. No reported studies to date have looked at the possible therapeutic role of taurine in preventing diabetic endothelial dysfunction. We therefore hypothesised that taurine would attenuate the microvascular changes associated with hyperglycaemia in an animal model through alteration of leucocyte–endothelial interactions. Male Sprague Dawley rats were randomised into control, hyperglycaemia, and taurine + hyperglycaemia groups. Taurine was gavaged (200 mg/kg) for 5 d prior to the experiment. Hyperglycaemia was established by intravenous infusion of 50% glucose. Blood glucose reached a steady state of 3 times baseline at 30 min. Using intravital microscopy leukocyte rolling, adhesion and transendothelial migration was determined in mesenteric postcapillary venules for 3 h. Intracellular adhesion molecule‐1 (ICAM‐1) was immunohistochemically graded using a scoring system to determine the expression in mesenteric tissue. Taurine pretreatment significantly attenuates leukocyte‐endothelial adhesion and transendothelial migration following acute hyperglycaemia but not leukocyte rolling velocity. The mechanism by which taurine protects against these effects is in part by inhibition of ICAM‐1 expression. Results at 120 min (n = 5/group) Control Hyperglycaemia Taurine + Hyperglycaemia Leukocyte rollingvelocity (m/s)49.5 (4.5)30.4 (6.4)45.4 (5.5)Leukocyteadhesion (/100(m)) 2.25 (1.70)*44.0 (10.5) 9.25 (2.3)*Transendothelialmigration (/field) 6.5 (1.3)*76.8 (20.7)12.25 (5.9)*Expression ofICAM‐1 (at 180 mins) 1.05 (0.40)* 2.9 (0.4) 1.1 (0.3)* Data are expressed as mean (SEM). Analysis with anova and post Scheffe hoc test. *P < 0.05 vs. Hyperglycaemia.