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Updated: Aug 19, 2026

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
Insulin-like growth factors inhibit podocyte apoptosis through the PI3 kinase pathway
Darren J Bridgewater1, Jackie Ho, Victor Sauro
1Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada.
Background:
Abnormal podocyte development and progressive podocyte injury have been implicated in a number of human kidney diseases. Factors necessary for regulating development and maintenance of this cell type are only beginning to emerge.
Methods:
To study the role of the insulin-like growth factor (IGF) system in regulating podocyte survival, we induced human fetal podocytes to undergo apoptosis. We demonstrated a significant increase in apoptosis when these cells were incubated in the presence of etoposide, as measured by DNA fragmentation and nuclear membrane condensation and blebbing.
Results:
Podocyte apoptosis was reduced to control levels when the cells were coincubated in the presence of IGF-1. We showed that the protective effect of IGFs in this cell type was mediated through the activation of the phosphatidylinositol 3'-kinase (PI3K) pathway. IGF-1 stimulation resulted in the formation of the insulin receptor substrate (IRS)-1-p85 complex, an increase in PI3 kinase activity, and activation of protein kinase B (AKT/PKB) and the bcl-2 family member bad. Incubation of the podocytes with inhibitors of the PI3 kinase pathway resulted in a loss of this IGF-1 protective effect.
Conclusion:
These data demonstrate an important role for the IGF system in fetal podocyte survival in vitro, and suggest potential mediators to slow or alleviate the loss or damage of the podocyte in progressive renal disease.
Insights
Insulin-like growth factor-1 (IGF-1) protects fetal podocytes from apoptosis by activating the phosphatidylinositol 3-kinase (PI3K) pathway. This finding suggests IGF-1 may help treat progressive kidney diseases.
Area of Science:
- Nephrology
- Cell Biology
- Endocrinology
Background:
- Podocyte injury is central to many kidney diseases.
- Understanding factors regulating podocyte survival is crucial.
Purpose of the Study:
- To investigate the role of the insulin-like growth factor (IGF) system in fetal podocyte survival.
- To elucidate the signaling pathways involved in IGF-mediated protection.
Main Methods:
- Human fetal podocytes were induced to undergo apoptosis using etoposide.
- Apoptosis was measured by DNA fragmentation and nuclear morphology.
- The effect of IGF-1 and PI3K pathway inhibitors was assessed.
Main Results:
- Etoposide significantly increased podocyte apoptosis.
- IGF-1 reduced apoptosis to control levels.
- IGF-1 protection was mediated by the PI3K/AKT/PKB pathway, involving IRS-1, p85, and bad.
Conclusions:
- The IGF system plays a vital role in fetal podocyte survival in vitro.
- IGF-1 may offer a therapeutic strategy to mitigate podocyte loss in progressive renal diseases.
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