PhD Scientific Days 2024

Theoretical and Translational Medicine III.

MIR-199 Has A Pro-Fibrotic Effect And Is Regulated By PPAR-γ Agonist In Renal Fibrosis

Előadó neve

Ms. Garmaa, Gantsetseg, MSc

Neptun code

WMR4UU

Előadó munkahelye

Institute of Translational Medicine, Semmelweis University, Budapest, Hungary

Előadó telefonszáma

06205720871

Előadó e-mail címe

gantsetseg.garmaa@gmail.com

Az előadás címe

MIR-199 Has A Pro-Fibrotic Effect And Is Regulated By PPAR-γ Agonist In Renal Fibrosis

Szerző(k) neve és munkahelye

Gantsetseg Garmaa¹, Krisztina Fazekas¹, Anna Manzéger¹, Miklós M. Mózes¹, Gábor Kökény¹

1: Institute of Translational Medicine, Semmelweis University, Budapest, Hungary

Bemutatás módja

Szóbeli

Szekció

Theoretical and Translational Medicine III.

Language of the presentation

English

Preferred session

Theoretical and Translational Medicine

Összefoglaló szövege

Background: The peroxisome proliferator-activated receptor-γ (PPARγ) agonists have been recently shown to suppress TGF-β signaling. Our research group has recently demonstrated that pioglitazone significantly ameliorates an established TGF-β induced renal fibrosis in transgenic mice by suppressing STAT3 and EGR1 transcription factors. However, the effect of pioglitazone on renal miR-199a-3p expression has not been investigated. We aimed to study 1) how chronic oral pioglitazone treatment would affect TGF-β–driven renal miRNA dysregulation in vitro and in vivo, and 2) how miR-199a-3p affects the fibrotic process in vitro.
Methods: Ten-week-old male C57BL/6 control (CTL, n=6) and TGF-β transgenic mice (TGFb, n=12, having elevated plasma TGF-β1 level) were used. CTL mice and half of TGFb mice received regular chow. The second half of transgenic mice received chow with pioglitazone (20mg/kg/day) for 5 weeks (TGFb+Pio, n=6), when the kidneys were evaluated. Primary tubular epithelial cells (TECs) were also isolated from C57BL/6 mice and treated with 10 ng/ml TGF-β1 and 30 nM miRNA inhibitor (anti-miR, n = 3) for 24 hours.
Results: Non-treated TGFb mice had a 4.7-fold and 2.8-fold type I and type III collagen mRNA overexpression compared to controls, respectively. This was accompanied by a 3.9-fold miR-199a-3p overexpression. Chronic treatment with the PPARγ agonist pioglitazone reduced the expression of both collagens and miR-199 to control levels. The suppression of miR-199a-3p in vitro alleviated TGF-β1-induced fibrotic cell responses, as shown by downregulated fibronectin mRNA (Fn1) and protein expression by 30.2% (p<0.05) and by 4.3%, respectively. This was accompanied by reduced Acta2 (α-SMA) and Tgfb1 mRNA expressions by 30.2% and 17.5%, respectively (p<0.05).
Conclusion: According to our data, the PPARγ agonist pioglitazone can reduce the TGF-β induced dysregulation of miR-199 both in vitro and in vivo, which suggests its anti-fibrotic effects. Furthermore, miR-199 may contribute to the pro-fibrotic process by targeting fibronectin, which is also regulated by PPARγ agonist.
Funding: SE 250+ Excellence Ph.D. Scholarship to GG; Bolyai Scholarship of the Hungarian Academy of Sciences (BO/00304/20/5 to GK); ÚNKP Bolyai+ Scholarship from the NRDI Office (ÚNKP-22-5/202206201434KG to GK).

University

Semmelweis University

Supervisor

Gábor Kökény

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6476

Start

15:45

End

15:55