Tubular Cytoplasmic Expression of Zinc Finger Protein SNAI1 in Renal Transplant Biopsies: A Sign of Diseased Epithelial Phenotype?

Détails

ID Serval
serval:BIB_D7AA443A9F92
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Tubular Cytoplasmic Expression of Zinc Finger Protein SNAI1 in Renal Transplant Biopsies: A Sign of Diseased Epithelial Phenotype?
Périodique
The American journal of pathology
Auteur(s)
Prunotto M., Chaykovska L., Bongiovanni M., Frattini M., Cagarelli T., Weibel F., Bruschi M., de Herreros A.G., Moll S.
ISSN
1525-2191 (Electronic)
ISSN-L
0002-9440
Statut éditorial
Publié
Date de publication
01/2017
Peer-reviewed
Oui
Volume
187
Numéro
1
Pages
55-69
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
The aim of the present study was to analyze in vivo the role of zinc finger protein SNAI1 (SNAI1) on renal fibrosis. Unilateral ureteral obstruction injury was induced in Snai1 knockout mice. Snai1 gene deletion was, however, only partial and could therefore not be correlated to reduced fibrosis. Expression of SNAI1 protein and epithelial-mesenchymal transformation markers was then assessed in human chronic allograft nephropathy biopsy specimens. Significant up-regulation of SNAI1 protein was detected within cytoplasm of proximal tubules localized, for some of them, near foci of fibrosis and tubular atrophy. No concomitant epithelial-mesenchymal transformation could, however, be demonstrated analyzing the expression of the fibroblast markers vimentin, α-smooth muscle actin, and S100A4. SNAI1 cytoplasmic up-regulation was particularly evident in biopsy specimens obtained from calcineurin inhibitor-treated patients, which might be because of, as suggested by in vitro experiments, a decrease of the proteasome chimotrypsin activity. Deeper analysis on chronic allograft nephropathy biopsy specimens suggested that SNAI1 cytoplasmic up-regulation was preceded by a transient increase of phosphorylated heat shock protein 27, p38 mitogen-activated protein kinase, and glycogen synthase kinase 3β. Concomitant down-regulation of the polyubuquitinylated conjugates was detected in SNAI1(+) tubules. Altogether, these results might suggest that calcineurin inhibitor-induced tubular SNAI1 protein cytoplasmic accumulation, possibly because of impaired SNAI1 proteasomal degradation and nuclear translocation, might be a sign of a diseased profibrotic epithelial phenotype.

Mots-clé
Allografts/drug effects, Animals, Biopsy, Calcineurin Inhibitors/pharmacology, Chronic Disease, Cytoplasm/metabolism, Dogs, Epithelial Cells/metabolism, Epithelial-Mesenchymal Transition/drug effects, Female, Fibrosis, Glycogen Synthase Kinase 3 beta/metabolism, HSP27 Heat-Shock Proteins/metabolism, Kidney Transplantation/adverse effects, Kidney Tubules/drug effects, Kidney Tubules/metabolism, Kidney Tubules/pathology, Madin Darby Canine Kidney Cells, Male, Mice, Knockout, Phenotype, Phosphorylation/drug effects, Proteasome Endopeptidase Complex/metabolism, Snail Family Transcription Factors/metabolism, Up-Regulation/drug effects, Ureteral Obstruction/pathology, Zinc Fingers, p38 Mitogen-Activated Protein Kinases/metabolism
Pubmed
Web of science
Création de la notice
25/11/2016 14:32
Dernière modification de la notice
20/08/2019 16:57
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