PhD Scientific Days 2024

Budapest, 9-10 July 2024

Poster Session F - Molecular Medicine 3.

Integrative method to identify therapeutic targets in the treatment of kidney fibrosis

Author(s)

Dr. Domonkos Pap1, Csenge Pajtók2, Apor Veres-Székely2,3, Beáta Szebeni2,3, Csenge Szász2, Péter Bokrossy2, Réka Zrufkó2, Szabó J. Attila2,3, Ádám Vannay2,3
1: Pediatric Center, MTA Center of Excellence, Semmelweis University, Budapest
2: Pediatric Center, MTA Center of Excellence, Semmelweis University, Budapest, Hungary
3: HUN-REN–SU Pediatrics and Nephrology Research Group, Budapest, Hungary

Text of the abstract

Introduction: Renal fibrosis is one of the main factor that leads to the gradual decline of renal function in patients with chronic kidney disease (CKD). Despite the urgent medical need, there is still no effective therapy to inhibit renal fibrosis.

Aims: To develop an integrative framework that helps the identification of possible target molecules and compounds which may have anti-fibrotic effects.

Methods: Comprehensive literature research was performed to identify those genes that have a role in renal fibrosis based on gene knockout (KO) animal studies. Moreover, genes whose expression correlates with the degree of renal fibrosis in the kidney of CKD patients were also collected. Finally, the overlapping set of the two lists was coupled with known compounds altering the function of the investigated genes in an anti-fibrotic manner.

Results: Based on KO animal studies we found 124 pro-fibrotic and 90 anti-fibrotic genes which were demonstrated to influence the amount of extracellular matrix (ECM) depositions in the kidney. Among them we identified 74 genes whose expression is correlated with the amount of ECM depositions in the kidney of patients with CKD. Using this method, more than 300 compounds were identified that affect these genes and may exert an anti-fibrotic effect.

Conclusion: We established a novel and effective method to identify drug targets and possible compounds that may have the potential to treat kidney fibrosis.

Fundings: Grants: K-142728, TKP2021-EGA-24, ELKH-POC-2022-024, ÚNKP-23-3-I-SE-36, ÚNKP-23-3-I-SE-42, ÚNKP-23-4-II-SE-29, ÚNKP-23-5-SE-15; Hungarian Academy of Sciences, János Bolyai Research Scholarship.