PhD Scientific Days 2020

Clinical Medicine IV. Lectures

The Role of PARK7 in Peritoneal Dialysis Associated Fibrosis

Előadó neve

Dr. Lévai, Eszter

Előadó munkahelye

Semmelweis University 1st Dept. of Pediatrics

Előadó telefonszáma

+36-30-5325-922

Előadó e-mail címe

levaiesz@gmail.com

Az előadás címe

The Role of PARK7 in Peritoneal Dialysis Associated Fibrosis

Szerző(k) neve és munkahelye

Eszter Lévai1, Beáta Szebeni1,2, István Márton Takács1, Csenge Pajtók1, Apor-Veres Székely1, Domonkos Pap1,2,, Zita Kovács1, József Mocsonaki1, Mária Bernáth1, György Reusz1, Attila Szabó1,2, Ádám Vannay1,2

1Semmelweis University 1st Dept. of Pediatrics
2MTA SE Pediatric and Nephrology Research Group

Szekció

Clinical Medicine IV. Lectures

Language of the presentation

English

Section, first choice

Clinical Medicine

Section, second choice

Molecular Sciences

Összefoglaló szövege

Introduction: During peritoneal dialysis (PD) complications as peritoneal mesothelial cell loss, progressive submesothelial fibrosis or vasculopathy are caused by the toxicity of dialysis solutions. Despite the unmet medical need there is no effective therapy for inhibiting peritoneal fibrosis. Recently, the role of PARK7 was demonstrated in the regulation of tissue fibrosis in various organs including the kidney and liver.

Aims: We aimed to prove the yet unknown presence, localisation and role of PARK7 in the peritoneum’s physiological and pathophysiological processes.

Method: Peritoneal dialysis effluents (PDE) of children receiving PD at the 1st Dept. of Pediatrics were collected. PARK7 level was measured in the PDEs by Western blot (Wb). In vitro experiments were carried out on human paerietal mesothelial cells (HPMC) and primary peritoneal fibroblasts (pPF) isolated from the peritoneum of children enrolled in our study. The effect of PDE on the viability of the different cells was assessed by MTT and LDH proliferation assays. Similarly, the effect of PDE on the mRNA expression of PARK7 was investigated by real-time RT-PCR. By implementing the chlorhexidine digluconate (CG)-induced mouse model of peritoneal fibrosis, we studied the localisation and amount of PARK7 by immunofluroescent staining (IF), Wb and RT-PCR respectively.

Results: The PARK7 level of PDEs differed among the individuals. PARK7 was present in the HPMCs and pPFs. HPMCs and pPFs proliferated and PARK7 expression increased following PDE-treatment. PARK7 immunoreactivity was present in the mesothelial layer and also submesothelially in the resident fibroblasts. While PARK7 expression decreased, the level of fibronectin increased in the parietal peritoneum of CG treated mice.
Conclusion: Regarding our results PARK7 have a potential role in the pathomechanism of PD induced peritoneal fibrosis. The decreased level of PARK7 might explain at least in part the progression of peritoneal fibrosis in the CG treated mice. Therefore it represents a promising therapeutic target to be able to lengthen the effective application of PD.

Grants: The project was founded by the following grants: ÚNKP 19-3-I-SE New National Excellence Program of the Ministry of Human Capacities, FIKP 61822-64912, 20382-3/2018 FEKUTSTRAT, STIA-18.

Additional Information

Supervisor: Attila J Szabó
e-mail: szabo.attila@med.semmelweis-univ.hu

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4745

Start

16:45

End

17:00

Authors (legacy)

Eszter Lévai1, Beáta Szebeni1,2, István Márton Takács1, Csenge Pajtók1, Apor-Veres Székely1, Domonkos Pap1,2,, Zita Kovács1, József Mocsonaki1, Mária Bernáth1, György Reusz1, Attila Szabó1,2, Ádám Vannay1,2

1Semmelweis University 1st Dept. of Pediatrics
2MTA SE Pediatric and Nephrology Research Group