Correlation between PKB/Akt, GSK‑3β expression and tubular epithelial‑mesenchymal transition in renal allografts with chronic active antibody‑mediated rejection

Yan,Qiang; Luo,Hao; Wang,Baoyao; Sui,Weiguo; Zou,Guimian; Chen,Huaizhou; Zou,Hequn

doi:10.3892/etm.2017.4261

Correlation between PKB/Akt, GSK‑3β expression and tubular epithelial‑mesenchymal transition in renal allografts with chronic active antibody‑mediated rejection

Authors:
- Qiang Yan
- Hao Luo
- Baoyao Wang
- Weiguo Sui
- Guimian Zou
- Huaizhou Chen
- Hequn Zou
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Affiliations: Department of Nephrology, Guilin 181st Hospital, Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi 541002, P.R. China, Department of Oncology, No. 454 Hospital of the PLA, Nanjing, Jiangsu 210002, P.R. China, Department of Nephrology, Institute of Nephrology and Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, P.R. China
Published online on: March 24, 2017 https://doi.org/10.3892/etm.2017.4261
Pages: 2217-2224
Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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