ArticleHistology and histopathology2020
p66Shc regulates podocyte autophagy in high glucose environment through the Notch-PTEN-PI3K/Akt/mTOR pathway.
Article in Histology and histopathology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- PTEN modulates mitochondrial dysfunction in podocytes via the PINK1/Parkin signal pathway.Translational pediatrics · 2026Article
- C3a/C3aR axis is involved in diabetic kidney injury by regulating podocyte mitophagy in diabetic nephropathy.International journal of molecular medicine · 2025Article
- mTOR pathway: A key player in diabetic nephropathy progression and therapeutic targets.Genes & diseases · 2025Review
- ER-α36 prevents high glucose-induced cellular senescence and apoptosis in renal tubular cell.Frontiers in endocrinology · 2025Article
- Notch signaling in diabetic kidney disease: recent progress.Frontiers in endocrinology · 2025Review
- Senolytic combination of dasatinib and quercetin protects against diabetic kidney disease by activating autophagy to alleviate podocyte dedifferentiation via the Notch pathway.International journal of molecular medicine · 2024Article
- The p66International journal of molecular sciences · 2023Review
- Qizhi Jiangtang capsule activates podocyte autophagy in diabetic kidney disease by inhibiting phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathways.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2023Article
- Redox regulation in diabetic kidney disease.American journal of physiology. Renal physiology · 2023Review
- Mitochondrial Oxidative Stress and Cell Death in Podocytopathies.Biomolecules · 2022Review
- The Role of p66Shc in Diabetes: A Comprehensive Review from Bench to Bedside.Journal of diabetes research · 2022Review
- Grape seed proanthocyanidin extract targets p66Shc to regulate mitochondrial biogenesis and dynamics in diabetic kidney disease.Frontiers in pharmacology · 2022Article
- Drug-induced thrombotic microangiopathy: An updated review of causative drugs, pathophysiology, and management.Frontiers in pharmacology · 2022Review
- The critical role of dysregulated autophagy in the progression of diabetic kidney disease.Frontiers in pharmacology · 2022Review
- NEDD4 E3 ubiquitin protein ligase serves an important role in cutaneous melanoma occurrence and development.Experimental and therapeutic medicine · 2021Article
- ADAMTS-13-regulated nuclear factor E2-related factor 2 signaling inhibits ferroptosis to ameliorate cisplatin-induced acute kidney injuy.Bioengineered · 2021Article
- Sirt3 promotes the autophagy of HK‑2 human proximal tubular epithelial cells via the inhibition of Notch‑1/Hes‑1 signaling.Molecular medicine reports · 2021Article
- Epidermal Growth Factor Protects Against High Glucose-Induced Podocyte Injury Possibly via Modulation of Autophagy and PI3K/AKT/mTOR Signaling Pathway Through DNA Methylation.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Article
- Role of Impaired Nutrient and Oxygen Deprivation Signaling and Deficient Autophagic Flux in Diabetic CKD Development: Implications for Understanding the Effects of Sodium-Glucose Cotransporter 2-Inhibitors.Journal of the American Society of Nephrology : JASN · 2020Review
- Yu Nu Compound Regulates Autophagy and Apoptosis Through mTOR in vivo and vitro.Diabetes, metabolic syndrome and obesity : targets and therapy · 2020Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND AND
aimsAutophagy has been found to be involved in podocyte injury, which is a key factor in the progression of diabetic kidney disease (DKD). p66Shc is an important protein adaptor that regulates production of reactive oxygen species (ROS) and induction of apoptosis, and is a novel biomarker for oxidative damage of renal tubules. Our preliminary studies showed that p66Shc expression in podocytes of DKD patients is increased, while autophagic flux and podocyte number is decreased in DKD patients. The mechanism by which p66Shc may regulate podocyte autophagy and injury remains unknown. The present study aimed to investigate the molecular function of p66Shc under high glucose condition and its possible therapeutic utility in DKD.
methodsWe histologically evaluated kidney injury in a streptozocin (STZ)-induced mouse model of diabetes using HE, PAS, PASM, and Masson staining and assessed glomerular structure by transmission electron microscopy. The apoptosis rate of high glucose-treated podocytes was assessed by TUNEL and Annexin V/PI staining. Markers of podocyte autophagy were measured by immunofluorescence and western blotting. DHE/ET fluorescence quantification was used for ROS detection and quantification.
resultsUrine creatinine, serum creatinine, urinary microalbumin, and p66Shc expression were significantly increased in STZ-induced diabetic mice. Cultured MPC5 podocytes subjected to high glucose showed reduced viability, and p66Shc overexpression further accelerated apoptosis. p66Shc knockdown enhanced HG-induced autophagy, while p66Shc overexpression reduced the expression of PTEN and increased the expression of mTOR and phospho-mTOR. LC3 protein expression was higher in cells with p66Shc knockdown, indicating that activation of p66Shc inhibits podocyte autophagy. DAPT, an inhibitor of the Notch pathway, downregulated the expression of p66Shc.
conclusionThese findings indicate that p66Shc inhibits podocyte autophagy and induces apoptosis through the Notch -PTEN-PI3K/Akt/ mTOR signaling pathway in high glucose environment, providing novel evidence for its potential role in DKD treatment.
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