title: Indoxyl sulfate upregulates prorenin expression via nuclear factor-κB p65, signal transducer and activator of transcription 3, and reactive oxygen species in proximal tubular cells.
abstract: We have recently found that indoxyl sulfate induces prorenin expression in proximal tubular cells. The present study aimed to determine whether nuclear factor-κB (NF-κB) p65, signal transducer and activator of transcription 3 (Stat3), and reactive oxygen species are involved in indoxyl sulfate-induced prorenin expression in cultured human proximal tubular cells (HK-2 cells). Effects of indoxyl sulfate on prorenin expression were determined using HK-2 cells with small interfering RNAs (siRNAs) specific to NF-κB p65 and Stat3, N-acetylcysteine, an antioxidant, and diphenyleneiodonium, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase. Indoxyl sulfate increased prorenin expression in HK-2 cells. siRNAs specific to NF-κB p65 and Stat3 inhibited indoxyl sulfate-induced prorenin expression. Both N-acetylcysteine and diphenyleneiodonium suppressed indoxyl sulfate-induced prorenin expression. Indoxyl sulfate upregulates the expression of prorenin via NF-κB p65, Stat3, and reactive oxygen species in proximal tubular cells.
authors.affiliation: Department of Advanced Medicine for Uremia, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Advanced Medicine for Uremia, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Maimaiti
authors.initials: M
authors.lastname: Yisireyili
authors.affiliation: Department of Advanced Medicine for Uremia, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hidehisa
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: Department of Advanced Medicine for Uremia, Nagoya University Graduate School of Medicine, Nagoya, Japan; Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Hwee-Yeong
authors.initials: HY
authors.lastname: Ng
authors.affiliation: Department of Advanced Medicine for Uremia, Nagoya University Graduate School of Medicine, Nagoya, Japan; Faculty of Health and Nutrition, Shubun University, Ichinomiya, Aichi, Japan. Electronic address: tniwa@med.nagoya-u.ac.jp.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Niwa
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D007200:Indican / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012083:Renin / Q000187:drug effects / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; D012083:Renin; D007200:Indican