PhD Scientific Days 2026

Poster Session 2.B - Molecular Medicine

Src Family Kinases Hck, Fgr, and Lyn Drive Disease Progression in Experimental Immune Complex–Mediated Glomerulonephritis

Name of the presenter

Deli, Dorottya

Institute/workplace of the presenter

Semmelweis University School of Medicine, Department of Physiology

Authors

Dorottya Deli¹, Lukács Lesinszki¹, Viktória Flóra Szabó¹, Attila Mócsai¹
1: Department of Physiology, Semmelweis University, Budapest, Hungary

Text of the abstract

Introduction:In immune complex–mediated glomerulonephritis, circulating immune complexes are deposited along the glomerular basement membrane, leading to local inflammation and progressive deterioration of renal function. The signaling pathways involved in disease pathogenesis remain poorly understood.
Aims:The aim was to investigate the role of Src family tyrosine kinases expressed in myeloid cells (Hck, Fgr, and Lyn) in a model of immune complex–mediated glomerulonephritis, with particular emphasis on the individual contribution of each kinase.
Methods:Immune complex–mediated glomerulonephritis was induced using an accelerated nephrotoxic nephritis model. Animals were preimmunized with sheep IgG, followed by induction of glomerulonephritis using sheep serum raised against mouse glomeruli (nephrotoxic serum, NTS). Urine samples were collected every second day to monitor renal function, and blood and tissue samples were obtained at the end of the experiment. Renal function was assessed by measuring urinary albumin levels as well as urinary and plasma creatinine concentrations. Structural kidney damage and immune cell infiltration were analyzed by histological methods (PAS staining, immunohistochemistry), while the composition and activation status of renal immune cell populations were quantified by flow cytometry.
Results:NTS treatment induced severe glomerulonephritis in wild-type mice, characterized by marked proteinuria, elevated serum creatinine levels, crescentic glomerular lesions, glomerulosclerosis, and significant leukocyte infiltration. In line with our previous findings, Hck⁻/⁻Fgr⁻/⁻Lyn⁻/⁻ triple knockout mice were completely protected from disease development. Hck⁻/⁻ single knockout mice also exhibited significant protection, whereas Fgr⁻/⁻ and Lyn⁻/⁻ single knockout mice developed severe glomerulonephritis comparable to that observed in wild-type animals.
Conclusion:Src family tyrosine kinases expressed in myeloid cells, particularly Hck, play a critical role in the development and progression of immune complex–mediated glomerulonephritis. The kinases investigated in this study represent promising therapeutic targets for the treatment of immune complex–mediated glomerulonephritides.
Funding:Hungarian National Research, Development and Innovation Office(KKP-129954,TKP2021-EGA-24 and TKP2021-EGA-29)HUN-REN Hungarian Research Network(0207007).