Indoxyl sulphate induces oxidative stress and the expression of osteoblast-specific proteins in vascular smooth muscle cells

Gulinuer Muteliefu, Atsushi Enomoto, Ping Jiang, Masahide Takahashi, Toshimitsu Niwa

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Background. Previously, we demonstrated that indoxyl sulphate (IS), a uraemic toxin, induced aortic calcification in hypertensive rats. This study aimed to determine if IS induces the production of reactive oxygen species (ROS) and the expression of osteoblast-specific proteins in human aortic smooth muscle cells (HASMCs).Methods. In order to achieve these goals, HASMCs were incubated with IS. ROS were detected using probes with a fluorescence detector. The expression of alkaline phosphatase (ALP), osteopontin and organic anion transporters (OAT1, OAT3) was studied by western blotting. The expression of core binding factor 1 (Cbfa1), ALP, osteopontin and NADPH oxidases (Nox1, Nox2 and Nox4) was analysed by reverse transcription-polymerase chain reaction (RT-PCR). Knockdown of Nox4 was performed by RNA interference (RNAi).Results. IS induced ROS generation and the expression of Nox4, Cbfa1, ALP and osteopontin in HASMCs. A NADPH oxidase inhibitor and antioxidants inhibited IS-induced ROS production and mRNA expression of Cbfa1 and ALP. Knockdown of Nox4 using small interfering RNA (siRNA) inhibited IS-induced ROS production and mRNA expression of Cbfa1, ALP and osteopontin. OAT3 was expressed in HASMCs.Conclusions. IS induces ROS generation by upregulating Nox4, and the expression of osteoblast-specific proteins such as Cbfa1, ALP and osteopontin in HASMCs.

Original languageEnglish
Pages (from-to)2051-2058
Number of pages8
JournalNephrology Dialysis Transplantation
Volume24
Issue number7
DOIs
Publication statusPublished - 07-2009

All Science Journal Classification (ASJC) codes

  • Nephrology
  • Transplantation

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