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Updated: May 6, 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
Interplay between the Notch and PI3K/Akt pathways in high glucose-induced podocyte apoptosis
Xiao-Mei Wang1, Min Yao, Shu-Xia Liu
1Dept. of Pathology, Third Hospital, Hebei Medical Univ., No. 139 Ziqiang Rd., Shijiazhuang, Hebei, China 050051. alan846829@163.com.
Abstract:
Podocyte apoptosis contributes to the pathogenesis of diabetic nephropathy (DN). However, the mechanisms that mediate high glucose (HG)-induced podocyte apoptosis remain poorly understood. Conditionally immortalized mouse podocytes were cultured in HG medium. A chemical inhibitor or a specific short-hairpin RNA (shRNA) vector was used to inhibit the activation of the Notch pathway and the PI3K/Akt pathway in HG-treated podocytes. Western blotting and real-time PCR were used to evaluate the levels of Notch, PI3K/Akt, and apoptotic pathway signaling. The apoptosis rate of HG-treated podocytes was assessed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling and annexin V/propidium iodide staining. In HG-treated podocytes, PI3K/Akt pathway activation prevented podocyte apoptosis in the early stage of HG stimulation and Notch pathway-induced podocyte apoptosis in the late stage of HG stimulation. The inhibition of the Notch pathway or the activation of the PI3K/Akt pathway prevented cell apoptosis in HG-treated podocytes. These findings suggest that the Notch and PI3K/Akt pathways may mediate HG-induced podocyte apoptosis.
Insights
High glucose triggers podocyte apoptosis in diabetic nephropathy. The PI3K/Akt and Notch pathways play crucial roles in this process, offering potential therapeutic targets for kidney disease.
Area of Science:
- Nephrology
- Molecular Biology
- Cell Biology
Background:
- Podocyte apoptosis is a key factor in diabetic nephropathy (DN) pathogenesis.
- The precise mechanisms underlying high glucose (HG)-induced podocyte apoptosis are not fully understood.
Purpose of the Study:
- To investigate the roles of the Notch and PI3K/Akt pathways in high glucose-induced podocyte apoptosis.
- To explore potential therapeutic interventions targeting these pathways in diabetic nephropathy.
Main Methods:
- Cultured conditionally immortalized mouse podocytes in high glucose medium.
- Utilized chemical inhibitors and short-hairpin RNA (shRNA) to modulate Notch and PI3K/Akt pathways.
- Assessed protein and gene expression via Western blotting and real-time PCR.
- Quantified podocyte apoptosis using TUNEL and Annexin V/PI staining.
Main Results:
- PI3K/Akt pathway activation inhibited podocyte apoptosis during early high glucose exposure.
- Notch pathway activation was implicated in podocyte apoptosis during later stages of high glucose exposure.
- Inhibiting the Notch pathway or activating the PI3K/Akt pathway reduced apoptosis in HG-treated podocytes.
Conclusions:
- The Notch and PI3K/Akt signaling pathways are critically involved in mediating high glucose-induced podocyte apoptosis.
- Modulating these pathways presents a potential therapeutic strategy for diabetic nephropathy.
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