PhD Scientific Days 2025

Poster Session III. - C: Molecular Medicine

The role of PARK7 in pulmonary fibrosis

Name of the presenter

Pap Domonkos

Institute/workplace of the presenter

Pediatric Center, MTA Center of Excellence, Semmelweis University, 1083 Budapest, Hungary; HUN-REN–SU Pediatrics and Nephrology Research Group, 1052 Budapest, Hungary

Authors

Domonkos Pap¹, Apor Veres-Székely¹, Beáta Szebeni¹, Csenge Szász², Péter Bokrossy², Réka Zrufkó², Attila J. Szabó¹, Ádám Vannay¹

1: Pediatric Center, MTA Center of Excellence, Semmelweis University, 1083 Budapest, Hungary; HUN-REN–SU Pediatrics and Nephrology Research Group, 1052 Budapest, Hungary
2: Pediatric Center, MTA Center of Excellence, Semmelweis University, 1083 Budapest, Hungary

Text of the abstract

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by excessive scarring, increasing breathlessness, and death within three to four years after diagnosis. Development of IPF is a result of an aberrant, repetitive alveolar epithelial injury, in which the oxidative stress plays a dominant role. Parkinson’s Diseases 7 (PARK7) molecule is a central mediator of the antioxidant defence mechanisms of various organs, however, its role in IPF and the underlying mechanisms is still unknown.

Aim: In the present study, we aimed to investigate the role and therapeutic potential of PARK7 in IPF.

Methods: Pulmonary expression of PARK7 was investigated in the bleomycin induced mouse model of lung fibrosis. The effect of pharmacological PARK7 activation with Comp23 on the synthesis of collagene and fibronectin (FN) and tissue density in the lungs was investigated in vivo. The effect of Comp23 treatment on oxidative damage (H2O2, bleomycin) induced death of lung alveolar epithelial cells (A549) was investigated in vitro.

Results: We found increased PARK7 expression in the fibrotic lung of mice treated with bleomycin. PARK7 activation with Comp23 treatment diminished the bleomycin induced collagene and FN levels, as well as the pathologic tissue density in the lungs. Comp23 treatment decreased the H2O2 and bleomycin induced oxidative stress and cell death of A549 cells.

Conclusion: Our data suggest that PARK7 protects the alveolar epithelial cells against oxidative damage thereby reducing the pathologic alterations in the lung leading to the development of IPF. Therefore, PARK7 may serve as a potential therapeutic target in the treatment of IPF.

Funding: EKÖP-2024-53; EKÖP-2024-160; EKÖP-2024-162; National Research, Development and Innovation Office – NKFIH, K-142728; Hungarian Academy of Sciences, János Bolyai Research Scholarship; TKP2021-EGA-24