PhD Scientific Days 2026

Theoretical and Translational Medicine 1.

Sigma-1 Receptor as a Novel Therapeutic Target in Diabetic Kidney Disease

Name of the presenter

Kállay, Hanga

Institute/workplace of the presenter

Semmelweis University, Pediatric Center

Authors

Hanga Kallay^1,2, Akos Toth^1,2, Dora B. Balogh¹, Marcell Cserhalmi¹, Alexandra Rozsahegyi^1,2, Lilla Lenart^1,2, Judit Hodrea^1,2, Attila J. Szabo², Adam Hosszu^1,2, Andrea Fekete^1,2
1: MTA-SE „Lendület” Momentum Diabetes Research Group, Budapest, Hungary
2: Pediatric Center, Semmelweis University, Budapest, Hungary

Text of the abstract

Introduction: Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease. Current treatments cannot halt the progression of renal injury, highlighting an urgent need for therapies targeting key disease mechanisms. Previously, we described the protective role of Sigma-1 receptor (S1R) agonist fluvoxamine (FLU) in acute kidney injury. Thus, we hypothesized a similar protective effect in DKD.
Aims: We designed this study to explore the potential renoprotective benefits of S1R activation in DKD.
Method: Diabetes mellitus was induced in male Wistar rats using streptozotocin, followed by a seven-week FLU treatment. Metabolic and renal parameters were assessed along with a histological analysis of glomerular damage (PAS) and tubulointerstitial fibrosis (Masson’s trichrome). The effects of inflammation and hypoxia were tested in lipopolysaccharide (LPS)- or hypoxia-induced human proximal tubular cells (HK-2). Cells were treated with FLU. Inflammatory and hypoxia markers were measured by RT-qPCR.
Results: FLU improved renal function and urinary biomarkers of tubular damage (KIM-1, NGAL) in DKD rats. In parallel, FLU reduced glomerular damage and fibrosis. FLU decreased LPS-induced TLR2, NFKB1, and IL6 expressions, as well as hypoxia-induced HIF1A, SLC2A1, VEGFA, and TGFB1 elevation in HK-2 cells.
Conclusion: S1R activation can slow DKD progression by modulating critical inflammatory, hypoxic, and fibrotic pathways. Thus, S1R may serve as a promising novel therapeutic target in DKD.
Funding: LP2021-3/2021, TKP2021-EGA-24, 2024-1.2.3-HU-RIZONT-2024-00056