PhD Scientific Days 2023

Molecular Sciences - Posters K

PARK7 as a New Therapeutic Target in Pulmonary Fibrosis

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 Comp-23 on the synthesis of extracellular matrix (ECM) components, including collagen-1 (Col1a1) and fibronectin (FN) in the lungs was investigated in vivo. The effect of Comp-23 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 Comp-23 treatment diminished the bleomycin induced Col1a1 and FN levels in the lungs. Comp-23 treatment decreased the H2O2 and bleomycin induced 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: This research was supported by National Research, Development and Innovation Office (NKFIH) K-142728; Semmelweis University, TKP2021-EGA-24, STIA-KFI-2021; Eötvös Loránd Research Network, ELKH-POC-2022-024; New National Excellence Program of the Ministry for Culture and Innovation from the Source of the National Research, Development and Innovation Fund, ÚNKP-22-4-II-SE-12, ÚNKP-22-5-SE-17; János Bolyai Research Scholarship by Hungarian Academic of Sciences

E-mail: pap.domonkos@med.semmelweis-univ.hu
Institute: Semmelweis University, Pediatric Center, Budapest, Hungary