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

Dora B Balogh1,2, Judit Hodrea1,2, Adar Saeed1,2

  • 1MTA-SE Lendület "Momentum" Diabetes Research Group, 1083 Budapest, Hungary.

International Journal of Molecular Sciences
|January 8, 2025
PubMed

Insights

Fluvoxamine (FLU), by activating the Sigma-1 receptor (S1R), shows promise in slowing diabetic kidney disease (DKD) progression. This study found FLU improved kidney function and reduced damage by targeting inflammation, hypoxia, and fibrosis.

Area of Science:

  • Nephrology
  • Pharmacology
  • Cell Biology

Background:

  • Diabetic kidney disease (DKD) is a major cause of chronic kidney disease with limited effective treatments.
  • Current therapies do not halt DKD progression, necessitating novel therapeutic strategies.
  • Sigma-1 receptor (S1R) activation with fluvoxamine (FLU) previously demonstrated protection against acute kidney injury.

Purpose of the Study:

  • To investigate the potential protective effects of fluvoxamine (FLU) in a rat model of diabetic kidney disease (DKD).
  • To explore the mechanisms underlying FLU's action, focusing on inflammation, hypoxia, and fibrosis pathways.

Main Methods:

  • DKD was induced in Wistar rats using streptozotocin, followed by a seven-week treatment with FLU.
  • Renal function, metabolic parameters, and kidney histology were assessed.
  • In vitro studies used human proximal tubular cells and rat kidney fibroblasts to examine FLU's effects on inflammation, hypoxia, and fibrosis.

Main Results:

  • Fluvoxamine (FLU) treatment improved renal function and significantly reduced glomerular damage and tubulointerstitial fibrosis in diabetic rats.
  • FLU mitigated inflammation by decreasing TLR4, IL6, and NFKB1 gene expression.
  • FLU moderated cellular responses to tubular hypoxia and suppressed TGF-β1-induced fibrotic processes.

Conclusions:

  • Activation of the Sigma-1 receptor (S1R) with fluvoxamine (FLU) demonstrates significant renoprotective effects in diabetic kidney disease (DKD).
  • FLU ameliorates DKD by modulating key pathways involved in inflammation, hypoxia, and fibrosis.
  • S1R activation represents a promising therapeutic target for slowing DKD progression and preserving kidney function.
Keywords:
Sigma-1 receptordiabetic kidney diseasefibrosis

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