title: Increased expression of intranuclear matrix metalloproteinase 9 in atrophic renal tubules is associated with renal fibrosis.
abstract: BACKGROUND
  Reduced 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.
  
  
  METHODS
  This 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.
  
  
  RESULTS
  Patients 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.
  
  
  CONCLUSIONS
  Interstitial 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.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Jen-Pi
authors.initials: JP
authors.lastname: Tsai
authors.forename: Jia-Hung
authors.initials: JH
authors.lastname: Liou
authors.forename: Wei-Tse
authors.initials: WT
authors.lastname: Kao
authors.forename: Shao-Chung
authors.initials: SC
authors.lastname: Wang
authors.forename: Jong-Da
authors.initials: JD
authors.lastname: Lian
authors.forename: Horng-Rong
authors.initials: HR
authors.lastname: Chang
mesh_terms: D000328:Adult; D002467:Cell Nucleus / Q000201:enzymology*; D005260:Female; D005355:Fibrosis / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000201:enzymology*; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis
chemical_list: D020780:Matrix Metalloproteinase 9