TY  - JOUR
AU  - Németh, Ágnes
AU  - Mózes, Miklós
AU  - Calvier, Laurent
AU  - Hansmann, Georg
AU  - Kökény, Gábor
TI  - The PPAR gamma agonist pioglitazone prevents TGF-beta induced renal fibrosis by repressing EGR-1 and STAT3
JF  - BMC NEPHROLOGY
J2  - BMC NEPHROL
VL  - 20
PY  - 2019
IS  - 1
PG  - 9
SN  - 1471-2369
DO  - 10.1186/s12882-019-1431-x
UR  - https://m2.mtmt.hu/api/publication/30731425
ID  - 30731425
AB  - BackgroundIt has been proposed that peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonists might reduce renal fibrosis, however, several studies had contradictory results. Moreover, the possible interaction of TGF-beta(1), PPAR gamma, and transcription factors in renal fibrosis have not been investigated. We hypothesized that oral pioglitazone treatment would inhibit TGF-beta-driven renal fibrosis and its progression, by modulating profibrotic transcription factors in TGF-beta(1) transgenic mice.MethodsMale C57Bl/6J mice (control, CTL, n=14) and TGF-beta overexpressing transgenic mice (TGF beta, n=14, having elevated plasma TGF-beta(1) level) were divided in two sets at 10weeks of age. Mice in the first set were fed with regular rodent chow (CTL and TGF beta, n=7/group). Mice in the second set were fed with chow containing pioglitazone (at a dose of 20mg/kg/day, CTL+Pio and TGF beta+Pio, n=7/group). After 5weeks of treatment, blood pressure was assessed and urine samples were collected, and the kidneys were analyzed for histology, mRNA and protein expression.ResultsTGF-beta(1) induced glomerulosclerosis and tubulointerstitial damage were significantly reduced by pioglitazone. Pioglitazone inhibited renal mRNA expression of all the profibrotic effectors: type-III collagen, TGF-beta(1), CTGF and TIMP-1, and alike transcription factors cFos/cJun and protein expression of EGR-1, and STAT3 protein phosphorylation.ConclusionsOral administration of PPAR gamma agonist pioglitazone significantly reduces TGF-beta(1)-driven renal fibrosis, via the attenuation of EGR-1, STAT3 and AP-1. This implies that PPAR gamma agonists might be effective in the treatment of chronic kidney disease patients.
LA  - English
DB  - MTMT
ER  -