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Indoxyl sulfate induces epithelial-to-mesenchymal transition in rat kidneys and human proximal tubular cells.

Bolati D, et al. Am J Nephrol. 2011.

Abstract

BACKGROUND/AIMS: Indoxyl sulfate (IS) is a uremic toxin that accelerates the progression of chronic kidney disease (CKD). This study aimed to determine if IS induces epithelial-to-mesenchymal transition (EMT) in the kidneys of hypertensive rats and human proximal tubular cells (HK-2).

METHODS: EMT was evaluated by immunohistochemistry, reverse transcription-polymerase chain reaction and immunoblotting of the epithelial markers E-cadherin and zonula occludens-1 (ZO-1), and the mesenchymal marker α-smooth muscle actin (α-SMA). Rat groups consisted of (1) Dahl salt-resistant normotensive rats (DN), (2) Dahl salt-resistant normotensive IS-administered rats (DN+IS), (3) Dahl salt-sensitive hypertensive rats (DH), and (4) Dahl salt-sensitive hypertensive IS-administered rats (DH+IS). HK-2 cells were incubated with or without IS.

RESULTS: In kidneys, DH rats showed reduced expression of E-cadherin and ZO-1, and enhanced expression of α-SMA compared with DN rats. DN+IS and DH+IS rats showed reduced expression of E-cadherin and ZO-1, and enhanced expression of α-SMA compared with DN and DH rats, respectively. DH+IS and DH rats showed increased Masson's trichrome-positive fibrosis areas compared with DH and DN, respectively. IS-treated HK-2 cells showed reduced expression of E-cadherin and ZO-1, and enhanced expression of α-SMA.

CONCLUSION: IS induces EMT in the kidneys of hypertensive rats and in human proximal tubular cells.

Copyright © 2011 S. Karger AG, Basel.

PMID

21849772 [PubMed - indexed for MEDLINE]

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