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Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
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SGLT2 inhibitor dapagliflozin limits podocyte damage in proteinuric nondiabetic nephropathy

Paola Cassis1, Monica Locatelli1, Domenico Cerullo1

  • 1IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.

JCI Insight
|August 10, 2018
PubMed

Insights

Sodium-glucose cotransporter 2 (SGLT2) inhibitors like dapagliflozin protect glomeruli from protein overload. This study reveals a novel mechanism where SGLT2 inhibitors maintain podocyte actin structure, suggesting potential for non-diabetic kidney disease.

Area of Science:

  • Nephrology
  • Pharmacology
  • Cell Biology

Background:

  • Sodium-glucose cotransporter 2 (SGLT2) inhibitors offer benefits beyond glucose control, including organ protection.
  • Renoprotective effects of SGLT2 inhibitors in diabetic kidney disease suggest potential in non-diabetic chronic kidney disease.

Purpose of the Study:

  • To investigate the renoprotective effects of dapagliflozin in a mouse model of protein-overload proteinuria.
  • To explore the underlying mechanism of SGLT2 inhibitor action on podocytes.

Main Methods:

  • Protein-overload proteinuria was induced in mice using bovine serum albumin (BSA).
  • Mice were treated with dapagliflozin or an ACE inhibitor as a control.
  • In vitro studies used cultured podocytes exposed to albumin to investigate SGLT2 function and mechanism.

Main Results:

  • Dapagliflozin significantly limited proteinuria, glomerular lesions, and podocyte dysfunction/loss.
  • SGLT2 expression was observed in podocytes and upregulated following BSA injection.
  • A novel mechanism involving the maintenance of actin cytoskeleton architecture by SGLT2 inhibitors in podocytes was identified.

Conclusions:

  • Dapagliflozin demonstrates glomerular protective effects in proteinuric kidney injury, comparable to ACE inhibitors.
  • SGLT2 inhibitors may offer a direct therapeutic benefit to podocytes via actin cytoskeleton stabilization.
  • Further clinical studies are warranted to evaluate SGLT2 inhibitors for proteinuric glomerular diseases without current effective treatments.
Keywords:
Chronic kidney diseaseNephrologyProtein traffic

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