Abstract
Context: Matrix metalloproteinases (MMPs) are involved in the remodelling of the glomerular
basement membrane (GBM) by tightly regulating the metabolism of extracellular matrix (ECM)
of the GBM.
Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, PubMed,
EBSCO, Scopus and Web of Science have been searched.
Results: Gelatinases (MMP-2 and MMP-9) are mainly found involved in the remodelling of GBM
and therefore this review focuses on these two MMPs and their action in nephrotic syndrome (NS),
which is a protein losing enteropathy occurring due to the loss of integrity of GBM. In addition to the
blood corpuscles, glomerular epithelial cells and mesangium are also expressing MMPs, and various
cytokines and growth factors are involved in addition to tissue inhibitors of metalloproteinases
(TIMPs) in regulating the metabolism of ECM via MMPs. While examining the results of
MMP activity and expression in NS, except diabetic nephropathy (DN), membranoproliferative
glomerulonephritis (MPGN) and hereditary NS where there was a clear down-regulation of MMP,
all the other types of NS showed conflicting results. Both suppression and induction of MMPs are
finally leading to GBM thickening, loss of integrity and proteinuria. Enhanced MMP activity leads
to increase in matrix turnover and accumulation of ECM remnants and apoptotic cells leading to
fibrosis. On the other hand, diminished expression of MMPs prevents the normal ECM turnover
and matrix accumulation. The review compiled the mechanisms of action of both downregulation
and upregulation of MMPs.
Conclusions: Imbalance of ECM metabolism due to varied expression levels and activities of MMPs
in different types of primary NS might contribute to the progression of nephropathies. Further
studies are required to identify the potential and usage of MMPs as a diagnostic/prognostic/
therapeutic tool.