Matrix Metalloproteinases in Renal Development and Disease

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Abstract
MMP are a large family of zinc-dependent matrix-degrading enzymes, which include the interstitial collagenases, stromelysins, gelatinases, elastases, and secreted, as well as membrane-type, RXKR containing MMP (13,14,15,16,17,18) (Table 1). They have been implicated in invasive cell behavior (18, 19), embryonic development (20,21,22), interstitial fibrosis (23), and glomerulosclerosis (24, 25). MMP share several structural and functional properties, which include pre/pro-peptide (26), hinge, hemopexin-like (except MMP-7), and catalytic zinc-binding domains (27, 28) (Figure 1). They synergistically degrade a broad range of ECM compounds. Of the currently known MMP, MMP-1, MMP-13, MMP-3, MMP-2, MMP-9, and MT-1-MMP have been extensively studied in the kidney. Four members in this group of collagenases, MMP-1, MMP-2, MMP-8 and MMP-13, share the ability to degrade fibrillar collagens (29,30,31). The resulting fragments denature spontaneously under physiologic temperatures, which then can be further degraded by other proteases.