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Indole-3-propionic acid suppresses indoxyl sulfate-induced expression of fibrotic and inflammatory genes in proximal tubular cells.
Yisireyili, Maimaiti; Takeshita, Kyosuke; Saito, Shinichi; Murohara, Toyoaki; Niwa, Toshimitsu.
Afiliação
  • Yisireyili M; Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Takeshita K; Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Saito S; Research Faculty of Agriculture, Hokkaido University, Sapporo, Japan.
  • Murohara T; Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Niwa T; Shubun University, Ichinomiya, Japan.
Nagoya J Med Sci ; 79(4): 477-486, 2017 11.
Article em En | MEDLINE | ID: mdl-29238104
Indoxyl sulfate (IS) induces fibrosis and inflammation in kidneys via oxidative stress through the induction of transforming growth factor-ß1 (TGF-ß1) and monocyte chemotactic protein-1 (MCP-1). Furthermore, IS is a potent endogenous agonist for aryl hydrocarbon receptor (AHR), which regulates the transcription of genes such as cytochrome P450 (CYP) 1A1. Indole-3-propionic acid (IPA) is an antioxidant and has been reported to be neuroprotective. We determined whether IPA suppresses IS-induced expression of AHR, CYP1A1, TGF-ß1, and MCP-1 in proximal tubular cells. The effects of IS on the expression of AHR, CYP1A1, TGF-ß1, and MCP-1 were studied using normotensive rats and hypertensive rats. The effects of IPA on IS-induced expression of AHR, CYP1A1, TGF-ß1, and MCP-1 were studied using proximal tubular cells (HK-2). Furthermore, the effects of IPA on IS-induced expression and phosphorylation of signal transducer and activator of transcription 3 (Stat3) were studied in HK-2 cells. Administration of IS induced the expression of AHR, CYP1A1, TGF-ß1, and MCP-1 in the tubular cells of rat kidneys. IPA significantly suppressed IS-induced mRNA and protein expression of AHR, CYP1A1, TGF-ß1, and MCP-1 in HK-2 cells. IPA suppressed the IS-induced expression and phosphorylation of Stat3 in HK-2 cells. Furthermore, knockdown of Stat3 inhibited the IS-induced mRNA and protein expression of AHR, CYP1A1, TGF-ß1, and MCP-1 in HK-2 cells. In conclusion, IPA suppressed the IS-induced expression of AHR, CYP1A1, TGF-ß1, and MCP-1 through suppression of Stat3 in proximal tubular cells. Thus, IPA suppresses IS-induced expression of fibrotic and inflammatory genes in proximal tubular cells.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Propionatos / Indicã / Inflamação / Túbulos Renais Proximais Limite: Animals / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Propionatos / Indicã / Inflamação / Túbulos Renais Proximais Limite: Animals / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article