@article{MTMT:30731425,
	title = {The PPAR gamma agonist pioglitazone prevents TGF-beta induced renal fibrosis by repressing EGR-1 and STAT3},
	url = {https://m2.mtmt.hu/api/publication/30731425},
	author = {Németh, Ágnes and Mózes, Miklós and Calvier, Laurent and Hansmann, Georg and Kökény, Gábor},
	doi = {10.1186/s12882-019-1431-x},
	journal-iso = {BMC NEPHROL},
	journal = {BMC NEPHROLOGY},
	volume = {20},
	unique-id = {30731425},
	issn = {1471-2369},
	abstract = {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.},
	year = {2019},
	eissn = {1471-2369},
	orcid-numbers = {Németh, Ágnes/0000-0002-4156-8853; Mózes, Miklós/0000-0001-9254-9890; Kökény, Gábor/0000-0002-0345-6914}
}