title: Matrix metalloproteinases and their role in the renal epithelial mesenchymal transition.
abstract: Tubular cell epithelial-mesenchymal transition (EMT) is a fundamental contributor to renal fibrosis. The aim of this study was to investigate the activity of different matrix metalloproteinases by immunohistochemistry and gel-zymography in a model of chronic canine kidney disease. Immunohistochemistry for antibodies against MMP-9, MMP-2, MMP-13, MMP-14 and TIMP-2 was performed on 28 renal biopsy specimens. Selected cases were chosen for gelatin zymography. In moderate and severe tubulo-interstitial damage, increased expression of MMP-2 was noted. A peculiar staining pattern for MMP-2 in variable-sized vesicles, corresponding to the area of basement membrane splitting, was observed. The immunoexpression of MMP-9 and TIMP-2 was reduced in the same cases, compared to control dogs. The splitting of the membrane suggests an active role of this gelatinase in the disruption of type-IV collagen, the main basement membrane component, confirmed by MMP2 gelatinolytic activity by gel-zymography. These data could provide the basis for clinical trials examining the potential benefits of selective MMP-2 inhibitors in dogs with chronic kidney disease.
authors.affiliation: Department of Public Health, Comparative Pathology and Veterinary Hygiene, University of Padova, Agripolis Legnaro, Padova, Italy. luca.aresu@unipd.it
authors.forename: L
authors.initials: L
authors.lastname: Aresu
authors.forename: S
authors.initials: S
authors.lastname: Benali
authors.forename: S
authors.initials: S
authors.lastname: Garbisa
authors.forename: E
authors.initials: E
authors.lastname: Gallo
authors.forename: M
authors.initials: M
authors.lastname: Castagnaro
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000201:enzymology; D024141:Collagen Type IV / Q000378:metabolism; D004285:Dogs; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D005355:Fibrosis / Q000473:pathology; D018093:Gelatinases / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology* / Q000201:enzymology* / Q000502:physiology; D007672:Kidney Cortex / Q000201:enzymology / Q000473:pathology; D007896:Leishmaniasis / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000502:physiology*; D016610:Tissue Embedding
chemical_list: D024141:Collagen Type IV; D018093:Gelatinases; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2