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Pitavastatin Exhibits Protective Effects on Podocytes Accompanied by BMP-7 Up-Regulation and Rho Suppression
Makoto Ohigashi1, Nobuyoshi Imai, Hiroe Toba
1Department of Clinical Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan.
Background/Aims:
Podocytes injury is involved in the development of diabetic nephropathy. This study was designed to confirm the reno- and podocyte-protective effects of pitavastatin in diabetic rats and clarify its mechanisms.
Methods:
Wistar rats were divided into 4 treatment groups: control, streptozotocin (STZ; 55 mg/kg)-induced diabetes, STZ with pitavastatin (10 mg/kg/day), and STZ with tempol (1 mmol/l).
Results:
STZ-induced diabetic rats exhibited increases in urinary protein excretion and plasma creatinine, and a decrease in creatinine clearance. Pitavastatin significantly improved these parameters without reducing cholesterol levels, whereas tempol did not. The treatment with STZ-enhanced renal fibrosis, mesangial proliferation, transforming growth factor (TGF)-β, MCP-1 and suppressed Rho in association with decrement of bone morphogenetic protein (BMP)-7 expression in renal cortex. Moreover, STZ decreased podocyte related factors, podocin and nephrin, and BMP-7 in podocytes. Pitavastatin significantly ameliorated all these indices. On the other hand, improvement by tempol was found only in TGF-β, MCP-1 and histological changes.
Conclusion:
Pitavastatin exhibited reno- and podocyte-protective effects accompanied by BMP-7 preservation and Rho suppression.
Insights
Pitavastatin protects kidneys and podocytes in diabetic rats by preserving bone morphogenetic protein-7 (BMP-7) and suppressing Rho. This offers a potential therapeutic strategy for diabetic nephropathy.
Area of Science:
- Nephrology
- Pharmacology
- Diabetology
Background:
- Diabetic nephropathy is a serious complication of diabetes.
- Podocyte injury is a key factor in its development.
- Understanding protective mechanisms is crucial for treatment.
Purpose of the Study:
- To investigate the reno- and podocyte-protective effects of pitavastatin in diabetic rats.
- To elucidate the underlying mechanisms of pitavastatin's action.
Main Methods:
- Streptozotocin (STZ)-induced diabetic Wistar rats were used.
- Treatment groups included control, STZ, STZ + pitavastatin, and STZ + tempol.
- Renal function, fibrosis, inflammatory markers, and podocyte-related factors were assessed.
Main Results:
- Pitavastatin improved urinary protein excretion and plasma creatinine in diabetic rats.
- Pitavastatin ameliorated renal fibrosis, mesangial proliferation, and inflammatory markers (TGF-β, MCP-1).
- Pitavastatin preserved podocyte-related factors (podocin, nephrin) and bone morphogenetic protein-7 (BMP-7), while suppressing Rho.
Conclusions:
- Pitavastatin demonstrates significant reno- and podocyte-protective effects in diabetic nephropathy.
- These effects are associated with BMP-7 preservation and Rho suppression.
- Pitavastatin may be a promising therapeutic agent for diabetic kidney disease.
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