Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Introduction: Most renal transplants ultimately fail secondary to chronic allograft nephropathy (CAN). The development of Epithelial to Mesenchymal Transition (EMT) in renal tubular epithelial cells has been described as a precursor to CAN. Vimentin, a cytoskeletal protein, is a member of the intermediate filament family of proteins and is expressed during EMT/CAN. What remains unknown is whether vimentin expression is required for EMT in renal grafts leading to CAN
Methods: The role of vimentin in CAN was determined in cultured human proximal renal tubular cells (HK-2) and mouse models of renal fibrosis. HK-2 cells were subjected to lentiviral-driven inhibition of vimentin expression. Cells were induced to undergo EMT via exposure to TGF-beta. Wound healing assays were used to determine EMT. Expression and translocation of beta-catenin was determined via western blotting, immunofluorescence, and mRNA quantification. Vimentin knockout mice (129 svs6 vim -/-) underwent unilateral ureteral obstruction (UUO). Kidneys were then harvested and analyzed via western blotting, immunofluorescence, and genomic analysis. All animal studies were IACUC approved.
Results: Western blotting analyses of mice undergoing UUO reveals an increase in soluble vimentin (1 week post-UUO) prior to the presence of soluble beta-catenin (2 weeks post-UUO). As expected interstitial collagen deposition was increased in control mice following UUO. However UUO in vim -/- mice revealed an earlier increase in soluble beta-catenin, but decreased development of fibrosis. E-cadherin and N-cadherin dynamics were also altered in vim -/- mice. Immunofluorescence analyses also revealed altered localization of beta-catenin in vim -/- mice undergoing UUO. In HK-2 cell lines undergoing EMT, vimentin inhibition also resulted in an increase in beta-catenin, with concomitant decrease in cellular migration during wound healing assay, consistent with our animal data. In addition, there were alterations in the presence and expression of cadherens junction proteins
Conclusion: Vimentin inhibition alters beta-catenin translocation as well as cadherens junction dynamics and results in decreased development of EMT/CAN. Therefore, vimentin expression is crucial for the development of EMT and fibrosis in mice via an alteration of the dynamics of b-catenin release from the cadherens junctions. These results provide insight into the role of vimentin in the steps leading to chronic graft loss following transplantation.
CITATION INFORMATION: Lopez-Soler R, Wang Z, Divanyan A. Vimentin Regulates ß-Catenin Translocation During Epithelial to Mesenchymal Transition in Renal Fibrosis. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Lopez-Soler R, Wang Z, Divanyan A. Vimentin Regulates ß-Catenin Translocation During Epithelial to Mesenchymal Transition in Renal Fibrosis. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/vimentin-regulates-catenin-translocation-during-epithelial-to-mesenchymal-transition-in-renal-fibrosis/. Accessed October 27, 2020.
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