PhD Scientific Days 2017

Oral Presentations: Basic Sciences II.

Pioglitazone effectively reduces renal interstitial fibrosis in TGF-ß transgenic mice

Előadó neve

Németh, Ágnes

Előadó munkahelye

Semmelwes University Institute of Pathophysiology

Előadó telefonszáma

06306315045

Előadó e-mail címe

nemeth.agnes.89@gmail.com

Az előadás címe

Pioglitazone effectively reduces renal interstitial fibrosis in TGF-ß transgenic mice

Szerző(k) neve és munkahelye

Ágnes Németh1, Krisztina Fazekas1, Mózes Miklós1, Gábor Kökény1
1 Semmelwes University Institute of Pathophysiology

Témacsoport

pathology and pathophysiology (non-oncology)

Szekció

Oral Presentations: Basic Sciences II.

Data of the presenter

Doctoral School: PhD School of Basic Medical Sciences
The title of the Program: Electrolyte balance in healthy and diseased regulation of blood pressure and circulation
The name of the Supervisor: Gábor Kökény MD, PhD
E-mail address: nemeth.agnes.89@gmail.com

Text of the abstract

Peroxisome proliferator-activated receptor-γ (PPARγ) agonists (pioglitazone, troglitazone) have been shown to reduce renal fibrosis in animal models of diabetic nephropathy, ischemia reperfusion injury or autosomal dominant polycystic kidney disease (ADPKD). However, pioglitazine failed to suppress unilateral ureter obstruction induced kidney fibrosis. Thus, the relationship between PPAR-γ and tubulointerstitial fibrosis is not clear yet. We aimed to study whether chronic pioglitazone treatment could counteract the profibrotic renal effect of elevated circulating TGF-β in transgenic mice.
Ten week old male C57Bl6 control and TGF-β transgenic mice (with elevated circulating TGF-β1 level) were divided in two sets. The first set of mice received regular chow (C and TGFb, n=4/group). The second set of mice were treated orally with pioglitazone (20mg/kg/day) for 5 weeks (C+Pio and TGFb+Pio, n=7-10/group). At 15 weeks of age, kidneys were harvested for histology and mRNA expression analyses. Data were analyzed using two-way ANOVA followed by Sidak’s multiple comparison test.
Pioglitazone reduced TGF-ß induced glomerulosclerosis by 30% (p<0.05) and the tubulointerstitial damage index by 50% (p<0.01). Although renal TGF-ß mRNA expression remained unaltered after pioglitazone treatment, CTGF expression decreased by 50% in TGFb-Pio kidneys (C: 1.0+/-0.2, C+Pio:0.7+/-0.2, TGFb:1.7+/-0.9,TGFb+Pio:0.8+/-0.3, p<0.05). Accordingly, the renal expression of type-III collagen was reduced 3-fold (C: 1.0+/-0.3, C+Pio:1.1+/-0.2, TGFb:2.8+/-0.8,TGFb+Pio:1.1+/-0.4, p<0.001) in pioglitazone treated TGFb mice. Interestingly, type-IV collagen mRNA expression did not differ between the groups.
We conclude that chronic pioglitazone administration can effectively reduce the profibrotic effect of elevated circulating TGF-ß in the renal interstitium, and to less extent in the glomeruli. Our results might help to clarify the relationship between PPAR-g and tubulointerstitial fibrosis.

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1105

Authors (legacy)

Ágnes Németh1, Krisztina Fazekas1, Mózes Miklós1, Gábor Kökény1
1 Semmelwes University Institute of Pathophysiology