Chronic antibody-mediated rejection (ABMR) is a major cause of the transplant renal interstitial fibrosis and transplanted kidney epithelial cell transdifferentiation is one of the main mechanisms. The transforming growth factor (TGF)-β1/integrin-linked kinase (ILK) signaling pathway has a significant role in the epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells; however, the molecular mechanisms of this process have remained elusive. The present study confirmed that Akt and glycogen synthase kinase (GSK)-3β, as TGF-β1 downstream signaling factors, are involved in fibrotic processes caused by kidney disease, which, however, has been rarely reported in the kidney transplant field. Based on the Banff 2009 standard, transplanted kidney specimens were classified according to the fibrosis level. The results showed that with the reduction of the interstitial fibrosis level, E-cadherin expression was gradually reduced, while α-smooth muscle actin expression progressively increased. The expression of Akt and GSK-3β in normal human kidney tissue was not obvious but showed a marked increase with the aggravation of the interstitial fibrosis level, which confirmed the occurrence of EMT during the fibrosis process, and that phosphorylated (p)-Akt and GSK-3β have an important role in the EMT process in the transplanted kidney. A correlation analysis of p-Akt, GSK-3β, TGF-β1 and ILK suggested that overexpression of p-Akt and GSK-3β may induce and mediate the transdifferentiation of renal tubular epithelial cells to myofibroblasts and that this proceeds via TGFβ1/ILK signaling pathways.
Keywords: E-cadherin; chronic active antibody-mediated rejection; epithelial-mesenchymal transition; glycogen synthase kinase 3β; interstitial fibrosis and tubular atrophy; protein kinase B; transforming growth factor beta1; transplantation.