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Open AccessReview

The Many Faces of Matrix Metalloproteinase-7 in Kidney Diseases

by Zhao Liu 1, Roderick J. Tan 2 and Youhua Liu 1,3,*
1
State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
2
Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
3
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(6), 960; https://doi.org/10.3390/biom10060960
Received: 1 May 2020 / Revised: 19 June 2020 / Accepted: 22 June 2020 / Published: 25 June 2020
(This article belongs to the Special Issue Matrix Metalloproteinases in Health and Disease)
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. View Full-Text
Keywords: matrix metalloproteinase-7; fibrosis; proteinuria; acute kidney injury; chronic kidney disease; apoptosis matrix metalloproteinase-7; fibrosis; proteinuria; acute kidney injury; chronic kidney disease; apoptosis
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Liu, Z.; Tan, R.J.; Liu, Y. The Many Faces of Matrix Metalloproteinase-7 in Kidney Diseases. Biomolecules 2020, 10, 960.

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