The Many Faces of Matrix Metalloproteinase-7 in Kidney Diseases

• Published in: Biomolecules (Basel, Switzerland) Vol. 10; no. 6; p. 960
• Main Authors: Liu, Zhao, Tan, Roderick J., Liu, Youhua
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25.06.2020; MDPI
• Subjects: acute kidney injury; Animals; Apoptosis; Binding sites; Biomarkers; Biomarkers - metabolism; Biopsy; Cell growth; Cell proliferation; chronic kidney disease; Diabetes; E-cadherin; Endopeptidases; Extracellular matrix; FasL protein; Fibrosis; Health aspects; Homeostasis; Humans; Kidney diseases; Kidney Diseases - enzymology; Kidney Diseases - pathology; Matrilysin; Matrix metalloproteinase; Matrix Metalloproteinase 7 - genetics; Matrix Metalloproteinase 7 - metabolism; matrix metalloproteinase-7; Mesenchyme; Metalloproteinase; Metalloproteins; Pathogenesis; Peptides; Physiological aspects; Proenzymes; Proteins; Proteinuria; Proteolysis; Review; Therapeutic applications; Transcription; Wnt protein; β-Catenin; United States; apoptosis; chronic kidney disease; acute kidney injury; fibrosis; proteinuria; matrix metalloproteinase-7
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom10060960

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.