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• W2099466528 abstract "Background. Hypoxia and inflammation, an unavoidable milieu for renal tubular cells during the development of renal fibrosis, reportedly up-regulate production of plasminogen activator inhibitor-1 (PAI-1), a promoter of tissue fibrosis. Peroxisome proliferator-activated receptor (PPAR)-γ agonists may modulate renal fibrosis progression via their anti-inflammatory effects in a PPAR-γ-dependent or -independent manner. However, no information is known about the effects of PPAR-γ agonists on PAI-1 expression in human proximal renal tubular cells (HPTECs) under hypoxia and/or inflammation. Methods. Confluent HPTECs were exposed to normoxia (18% O 2 ), hypoxia (1% O 2 ) and/or TNF-α at 10 ng/mL for up to 48 h. The cells were incubated with two PPAR-γ ago- nists, 15-deoxy-delta 12,14-prostaglandin J2 (15d-PGJ2) and pioglitazone. Precise amounts of PAI-1 mRNA and protein were measured by TaqMan quantitative PCR and immunoassay, respectively. PPAR response element (PPRE) activity induced by 15d-PGJ2 was measured by transfection with PPRE-luciferase construct. Results. Basal PAI-1 was significantly increased, in a dose-dependent manner, by 15d-PGJ2. It also enhanced hypoxia-, TNF-α- and hypoxia plus TNF-α-stimulated PAI-1 expression at the mRNA and protein levels. Pioglitazone had no influence on PAI-1 protein production. Although 15d-PGJ2 enhanced PPRE activity significantly in the HPTECs expressing PPAR-γ, a specific inhibitor for PPAR-γ, GW9662, did not diminish 15d-PGJ2-induced PAI-1 expression. In contrast, a non-selective tyrosine kinase (TK) inhibitor, genisteine or a MEK1 (MAPK kinase) inhibitor, PD98059, inhibited 15d-PGJ2-induced PAI-1 production completely. Conclusions. The endogenous PPAR-γ agonist, 15d-PGJ2, increased PAI-1 expression independently of PPAR-γ via the activation of TK or MAP kinase in HPTECs and may act as an enhancer of PAI-1 production in the kidney under hypoxic and inflammatory conditions." @default.
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• W2099466528 date "2008-04-02" @default.
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• W2099466528 title "A natural PPAR- agonist, 15-deoxy-delta 12,14-prostaglandin J2, may act as an enhancer of PAI-1 in human proximal renal tubular cells under hypoxic and inflammatory conditions" @default.
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• W2099466528 doi "https://doi.org/10.1093/ndt/gfn139" @default.
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