Abstract
Our recent study suggested that peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist attenuates inflammatory response in activated tubular epithelial cells in IgA nephropathy (IgAN). Here, we explore thiazolidinediones as new therapeutic additives to established treatment regime of renin angiotensin blockade in IgAN. Human proximal tubular epithelial cells (PTEC) were pretreated with PPAR-gamma agonist, rosiglitazone, and/or angiotensin II (AngII) type 1 receptor (ATR1) blocker (ARB), losartan, followed by activation with the conditioned medium collected from human mesangial cells incubated with pIgA1 (IgA-HMC) from patients with IgAN. IgA-HMC conditioned medium up-regulated expression of ICAM-1, IL-6 and ATR1 and activated NF-kappaB and ERK1/2 in PTEC. Dual treatment of rosiglitazone and losartan provided synergistic effect in reducing ICAM-1, IL-6 and ATR1 expression and NF-kappaB and ERK1/2 activation induced by the conditioned media when compared with monotherapy. Our data suggest that rosiglitazone trans-represses AngII signaling and may offer additional potential when combined with ARB in treating IgAN.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiotensin II Type 1 Receptor Blockers / pharmacology
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Anilides / pharmacology
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Blotting, Western
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Cells, Cultured
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Culture Media, Conditioned / metabolism
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Culture Media, Conditioned / pharmacology
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Epithelial Cells / cytology
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Epithelial Cells / drug effects
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Epithelial Cells / metabolism*
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Female
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Gene Expression Regulation / drug effects
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Glomerulonephritis, IGA / immunology
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Glomerulonephritis, IGA / metabolism
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Glomerulonephritis, IGA / physiopathology*
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Humans
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Immunoglobulin A / immunology
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Immunoglobulin A / pharmacology
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Intercellular Adhesion Molecule-1 / genetics
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Intercellular Adhesion Molecule-1 / metabolism
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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Kidney Tubules / cytology
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Losartan / pharmacology
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Male
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Mesangial Cells / cytology
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Mesangial Cells / immunology
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Mesangial Cells / metabolism
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NF-kappa B / metabolism
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PPAR gamma / agonists
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PPAR gamma / physiology*
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Receptor Cross-Talk
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Receptor, Angiotensin, Type 1 / genetics
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Receptor, Angiotensin, Type 1 / metabolism
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Receptor, Angiotensin, Type 1 / physiology*
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Reverse Transcriptase Polymerase Chain Reaction
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Rosiglitazone
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Signal Transduction / drug effects
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Thiazolidinediones / pharmacology
Substances
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2-chloro-5-nitrobenzanilide
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Angiotensin II Type 1 Receptor Blockers
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Anilides
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Culture Media, Conditioned
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Immunoglobulin A
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Interleukin-6
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NF-kappa B
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PPAR gamma
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Receptor, Angiotensin, Type 1
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Thiazolidinediones
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Rosiglitazone
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Intercellular Adhesion Molecule-1
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Extracellular Signal-Regulated MAP Kinases
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Losartan