Abstract
Matrix metalloproteinase-7 (MMP-7) is a secreted zinc-dependent endopeptidase that is implicated in regulating kidney homeostasis and diseases. MMP-7 is produced as an inactive zymogen, and proteolytic cleavage is required for its activation. MMP-7 is barely expressed in normal adult kidney but upregulated in acute kidney injury (AKI) and chronic kidney disease (CKD). The expression of MMP-7 is transcriptionally regulated by Wnt/β-catenin and other cues. As a secreted protein, MMP-7 is present and increased in the urine of patients, and its levels serve as a noninvasive biomarker for predicting AKI prognosis and monitoring CKD progression. Apart from degrading components of the extracellular matrix, MMP-7 also cleaves a wide range of substrates, such as E-cadherin, Fas ligand, and nephrin. As such, it plays an essential role in regulating many cellular processes, such as cell proliferation, apoptosis, epithelial-mesenchymal transition, and podocyte injury. The function of MMP-7 in kidney diseases is complex and context-dependent. It protects against AKI by priming tubular cells for survival and regeneration but promotes kidney fibrosis and CKD progression. MMP-7 also impairs podocyte integrity and induces proteinuria. In this review, we summarized recent advances in our understanding of the regulation, role, and mechanisms of MMP-7 in the pathogenesis of kidney diseases. We also discussed the potential of MMP-7 as a biomarker and therapeutic target in a clinical setting.
Highlights
Matrix metalloproteinase-7 (MMP-7), known as matrilysin-1, is one of the smallest secreted proteases of the MMP family, which consists of more than 20 structurally-related zinc-dependent endopeptidases with broad substrate specificity [1,2]
Kidney tissues from patients with IgA nephropathy (IgAN) show positive MMP-7 staining in renal tubular epithelia, fluids in the tubular lumen, and glomerular podocytes [12,21]
These findings indicate that uMMP-7 may hold promise as a noninvasive biomarker for kidney fibrosis and chronic kidney disease (CKD) progression
Summary
Matrix metalloproteinase-7 (MMP-7), known as matrilysin-1, is one of the smallest secreted proteases of the MMP family, which consists of more than 20 structurally-related zinc-dependent endopeptidases with broad substrate specificity [1,2]. .ThTehecDcDNNAAofoMf MMMP-P7-7enecnocdoedseas parportoetienincocnotnatianiinnigng262767amamininooacaicdids.s.StSrtuructcuturarlallyly, ,MMMMPP-7-7oonnlylyccoonnssiissttssooffaapprroo--ppeeppttiiddee ddoommaaiinn aanndd aa ccaattaallyyttiicc ddoommaaiinn ((FFiigguurree 11AA)),, wwhhiicchh sseeppaarraatteess iitt ffrroomm mmoosstt ootthheerr MMMMPPss tthhaatt ccoonnttaaiinn aann aaddddiittiioonnaall hhiinnggee rreeggiioonnaannddaahhememopopexeixni-nli-kliekedodmomainai[n1,[21,,126,1].6T].hTehcerycsrtyasltsatlrustcrtuucrteuorfeMofMMP-M7 Pco-7ntcaoinnitnagintihnegttwhoe tdwoomdaionms aaifnosreamfoernetmioennetdioinsesdhoiswsnhoinwFniginurFeig1uBr.e 1B. The activity of MMP-7 is regulated by a family of naturally occurring endogenous inhibitors known as tissue inhibitors of metalloproteinases (TIMPs). The expression of MMP-7 is transcriptionally regulated by different cues, the Wnt/β-catenin and transforming growth factor-β (TGF-β). The promoter of the human MMP-7 gene contains a TATA box, an activator protein 1 (AP-1) site, and T cell factor (TCF)-binding elements. As TGF-β is known to activate β-catenin signaling [19], it remains elusive whether TGF-β controls MMP-7 expression directly or via β-catenin indirectly
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
