Expression of β-catenin in regenerating renal tubules of cisplatin-induced kidney failure in rats

Abstract

Background

β-Catenin is a multi-functional protein involved in nephrogenesis and also plays important roles in renal injury. Here, the expression of β-catenin was investigated in the proximal renal tubular epithelial cells in cisplatin (CDDP)-induced acute kidney injury (AKI) and chronic kidney injury (CKI), because CDDP-induced renal lesions were characterized by proximal renal tubular epithelial degeneration/regeneration and subsequent interstitial fibrosis.

Methods

F344 rats were treated with CDDP. The expression of β-catenin and proliferative (Ki67) or fibrogenic [vimentin, α-smooth action (α-SMA)] markers was analyzed by immunolabeling.

Results

β-Catenin, vimentin and Ki67 were not seen in the proximal renal tubules of control rats. Interestingly, in CDDP-induced AKI, the regenerating proximal renal tubular epithelial cells reacting strongly with Ki67 expressed membranous or cytoplasmic β-catenin and also showed a positive reaction to vimentin but not to α-SMA. In CDDP-induced CKI, the epithelial cells of abnormally dilated or atrophied renal tubules did not react to β-catenin or Ki67, but showed positive reactions to vimentin and α-SMA. β-Catenin mRNAs were significantly increased in AKI and significantly decreased in CKI.

Conclusion

Newly expressed β-catenin in the proximal renal tubules after AKI may participate in functional regeneration. In CKI, epithelial cells of abnormal renal tubules did not express β-catenin but reacted to vimentin, and α-SMA might indicate the epithelial–mesenchymal transition (EMT) formation, because α-SMA is usually expressed in myofibroblasts forming via EMT. The presence or absence of β-catenin expression would become a marker for the EMT phenomenon in progressive renal fibrosis.

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Acknowledgements

This work was supported partly by the JSPS KAKENHI Grant Numbers 26292152 (to Yamate), by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS) from AMED under Grant Number JP18am0101123, and by the Ichiro Kanehara Foundation for the Promotion of Medical Science and Medical Care (The 31st International Student Grant to Karim).

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Correspondence to Jyoji Yamate.

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There are no conflicts of interest.

Ethical considerations

Animal experiments were carried out in accordance with the guidelines set by the Graduate School of Life and Environmental Sciences, Osaka Prefecture University. The protocol was approved by the ethical committee for the Care and Use of Experimental Animals of Osaka Prefecture University (Permit No. 21-16 and 25-85) and conformed to the Guidelines for the Conduct of Animal Experimentation of the Ministry of Health, Labor and Welfare Standards relating to the Care and Management of Experimental Animals and the Act on Welfare and Management of Animals, Japan. All efforts were made to minimize animal suffering. Specimens from humans were not used.

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Terada, N., Karim, M.R., Izawa, T. et al. Expression of β-catenin in regenerating renal tubules of cisplatin-induced kidney failure in rats. Clin Exp Nephrol 22, 1240–1250 (2018). https://doi.org/10.1007/s10157-018-1583-1

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Keyword

  • β-Catenin
  • Cisplatin
  • Rats
  • Regenerating renal tubular epithelial cells