title: Epithelial mesenchymal transition in the progression of renal disease in dogs.
abstract: Chronic kidney disease (CKD) in dogs is the final common pathway resulting from persistent renal injury and is characterized by progressive tubulointerstitial damage (TID). Pathogenesis of CKD is divided into an initial inflammatory phase with a predominantly mononuclear infiltrate followed by a fibrotic phase with increased numbers of fibroblasts and extracellular matrix deposition that causes a progressive reduction of functional parenchyma. Proteinuria is a common manifestation of renal diseases in dogs, and its role in the pathogenesis of CKD is still uncertain. Nevertheless, the degree of proteinuria in dogs correlates with TID progression. Increased protein filtration may have direct effects on tubular epithelial cells (TECs) that induce them to express the major histocompatibility complex type II, and thereby contribute to lymphocyte recruitment. Thus, an active pro-inflammatory role is proposed for TECs in TID progression. Moreover TECs are believed to actively participate in the mechanisms of renal fibrosis. Epithelial-Mesenchymal-Transition (EMT) of TECs in canine TID has been studied in the last decade. Down-regulation of adhesion molecules and loss of epithelial markers in TECs directly correlate with the severity of TID and with de novo expression of mesenchymal markers. Tubular basement membrane (TBM) disruption is an early EMT event. Increased activity of Matrix Metalloproteinase-2 and its co-localization with TBM splitting suggests an active role for the enzyme in inducing EMT. Processes occurring in canine CKD share many similarities with its human counterpart, making the dog a good model in which to examine the mechanisms of TID progression.
authors.affiliation: Department Comparative Biomedicine and Food Science, University of Padova, Legnaro, PD, Italy.
authors.forename: S L
authors.initials: SL
authors.lastname: Benali
authors.affiliation: Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, TX, USA.
authors.forename: G E
authors.initials: GE
authors.lastname: Lees
authors.affiliation: Department Comparative Biomedicine and Food Science, University of Padova, Legnaro, PD, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Castagnaro
authors.affiliation: Department Comparative Biomedicine and Food Science, University of Padova, Legnaro, PD, Italy. luca.aresu@unipd.it.
authors.forename: L
authors.initials: L
authors.lastname: Aresu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004285:Dogs; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D007674:Kidney Diseases / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology*; D011507:Proteinuria / Q000503:physiopathology