Increased Expression of Intranuclear Matrix Metalloproteinase 9 in Atrophic Renal Tubules Is Associated with Renal Fibrosis

Abstract

BackgroundReduced turnover of extracellular matrix has a role in renal fibrosis. Matrix metalloproteinases (MMPs) is associated with many glomerular diseases, but the histological association of MMPs and human renal fibrosis is unclear.MethodsThis is a retrospective study. Institutional Review Board approval was obtained for the review of patients’ medical records, data analysis and pathological specimens staining with waiver of informed consents. Specimens of forty-six patients were examined by immunohistochemical stain of MMP-9 in nephrectomized kidneys, and the association of renal expression of MMP-9 and renal fibrosis was determined. MMP-9 expression in individual renal components and fibrosis was graded as high or low based on MMP-9 staining and fibrotic scores.ResultsPatients with high interstitial fibrosis scores (IFS) and glomerular fibrosis scores (GFS) had significantly higher serum creatinine, lower estimated glomerular filtration rate (eGFR), and were more likely to have chronic kidney disease (CKD) and urothelial cell carcinoma. Univariate analysis showed that IFS and GFS were negatively associated with normal and atrophic tubular cytoplasmic MMP-9 expression and IFS was positively correlated with atrophic tubular nuclear MMP-9 expression. Multivariate stepwise regression indicated that MMP-9 expression in atrophic tubular nuclei (r = 0.4, p = 0.002) was an independent predictor of IFS, and that MMP-9 expression in normal tubular cytoplasm (r = −0.465, p<0.001) was an independent predictor of GFS.ConclusionsInterstitial fibrosis correlated with MMP-9 expression in the atrophic tubular nuclei. Our results indicate that renal fibrosis is associated with a decline of MMP-9 expression in the cytoplasm of normal tubular cells and increased expression of MMP-9 in the nuclei of tubular atrophic renal tubules.

microRNA-133b downregulation and inhibition of cell proliferation, migration and invasion by targeting matrix metallopeptidase-9 in renal cell carcinoma

“…MMP-9, a 92 kDa type IV collagenase, is regulated through formation of proenzyme complexes with endogenous TIMP-1. The spatial expression of MMP-9 in the kidney is complex and species specific (30). MMP-9 is mainly expressed in collecting duct cells and to a lesser extent in proximal tubule and podocytes of mice (31), in the proximal and distal tubules of monkeys (32), and in glomerular mesangial cells of humans (33).…”

Activation of Wnt5a‐Ror2 signaling associated with epithelial‐to‐mesenchymal transition of tubular epithelial cells during renal fibrosis

“…; Tsai et al . ), it is of interest to examine whether Wnt5a‐Ror2 signaling is also involved in induced expression of MMP‐9 .…”

“…Taken together, Wnt5a-Ror2 signaling appears to contribute to renal pathological features at least partly by TBM disruption via induced expression of MMP-2, during renal fibrosis. Because another member of MMPs, MMP-9, has also been shown to play a similar role in disrupting TBM during renal fibrosis (B€ ottinger & Bitzer 2002;Wang et al 2010;Tsai et al 2012), it is of interest to examine whether Wnt5a-Ror2 signaling is also involved in induced expression of MMP-9.…”

Tryptase compromises corneal epithelial barrier function

“…12,13 MMP9 is also involved in some eye disorders, such as dry eye 14 ; whether it is involved in the corneal barrier function is unknown. MMP9 is involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction and tissue remodelling, as well as in disease processes, such as arthritis, intracerebral haemorrhage and metastasis.…”

“…MMP9 is involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction and tissue remodelling, as well as in disease processes, such as arthritis, intracerebral haemorrhage and metastasis. 12,13 MMP9 is also involved in some eye disorders, such as dry eye 14 ; whether it is involved in the corneal barrier function is unknown.…”