Epithelial-mesenchymal transition (EMT) of renal tubular cells in canine glomerulonephritis.
Tubulo-interstitial fibrosis in dogs may result from primary injury to the interstitium or develop secondary to other renal diseases. As in human renal pathology, tubular epithelial cells (TEC) are believed to actively participate in the mechanisms of renal fibrosis. In this study, we examined the changes in the tubular epithelial component in two specific canine diseases. Immunohistochemistry showed the expression of the epithelial marker cytokeratin, the smooth muscle marker alpha-SMA, the mesenchymal marker vimentin and PCNA in 20 dogs with membranous glomerulonephritis and membrano-proliferative glomerulonephritis. Results showed that the loss of the epithelial marker in TEC was directly correlated to the grade of tubulo-interstitial disease present and independent of the type of glomerulonephritis. Varying degrees of vimentin positivity were detected in tubular epithelium in areas of inflammation, and low numbers of scattered alpha-SMA-positive cells were also observed. Immunohistochemistry showed that epithelial tubular cells lose their cytokeratin staining characteristics and transdifferentiate into cells exhibiting key mesenchymal immunophenotypic feature of vimentin-positive staining in both diseases investigated. The integrity of the tubular basement membrane is likely to be fundamental in maintaining the epithelial phenotype of TEC. Animal models provide opportunities for investigating the pathogenesis of renal fibrosis in humans.
Aresu
Luca
L
Dipartimento di Patologia Animale, Università degli Studi di Torino, via L. Da Vinci 44, 10095 Grugliasco, TO, Italy. luca.aresu@unito.it
Rastaldi
Maria Pia
MP
Scanziani
Eugenio
E
Baily
James
J
Radaelli
Enrico
E
Pregel
Paola
P
Valenza
Federico
F
D000199:Actins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D004285:Dogs; D004847:Epithelial Cells / Q000473:pathology*; D005260:Female; D005355:Fibrosis; D005921:Glomerulonephritis / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D007633:Keratins / Q000378:metabolism; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D014746:Vimentin / Q000378:metabolism
D000199:Actins; D014746:Vimentin; D007633:Keratins
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