The PPARγ agonist pioglitazone prevents TGF-ß induced renal fibrosis by repressing EGR-1 and STAT3.
BMC Nephrol
; 20(1): 245, 2019 07 05.
Article
em En
| MEDLINE
| ID: mdl-31277592
ABSTRACT
BACKGROUND:
It has been proposed that peroxisome proliferator-activated receptor-γ (PPARγ) agonists might reduce renal fibrosis, however, several studies had contradictory results. Moreover, the possible interaction of TGF-ß1, PPARγ, and transcription factors in renal fibrosis have not been investigated. We hypothesized that oral pioglitazone treatment would inhibit TGF-ß-driven renal fibrosis and its progression, by modulating profibrotic transcription factors in TGF-ß1 transgenic mice.METHODS:
Male C57Bl/6 J mice (control, CTL, n = 14) and TGF-ß overexpressing transgenic mice (TGFß, n = 14, having elevated plasma TGF-ß1 level) were divided in two sets at 10 weeks of age. Mice in the first set were fed with regular rodent chow (CTL and TGFß, n = 7/group). Mice in the second set were fed with chow containing pioglitazone (at a dose of 20 mg/kg/day, CTL + Pio and TGFß+Pio, n = 7/group). After 5 weeks of treatment, blood pressure was assessed and urine samples were collected, and the kidneys were analyzed for histology, mRNA and protein expression.RESULTS:
TGF-ß1 induced glomerulosclerosis and tubulointerstitial damage were significantly reduced by pioglitazone. Pioglitazone inhibited renal mRNA expression of all the profibrotic effectors type-III collagen, TGF-ß1, CTGF and TIMP-1, and alike transcription factors cFos/cJun and protein expression of EGR-1, and STAT3 protein phosphorylation.CONCLUSIONS:
Oral administration of PPARγ agonist pioglitazone significantly reduces TGF-ß1-driven renal fibrosis, via the attenuation of EGR-1, STAT3 and AP-1. This implies that PPARγ agonists might be effective in the treatment of chronic kidney disease patients.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Transformador beta
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PPAR gama
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Fator de Transcrição STAT3
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Proteína 1 de Resposta de Crescimento Precoce
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Pioglitazona
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Nefropatias
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article