ArticleJournal of the American Society of Nephrology : JASN2011
The tuberin/mTOR pathway promotes apoptosis of tubular epithelial cells in diabetes.
Article in Journal of the American Society of Nephrology : JASN, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 74 citations in OpenAlex.
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- Eupatilin attenuates doxorubicin-induced cardiotoxicity by activating the PI3K-AKT signaling pathway in mice.Molecular and cellular biochemistry · 2024Article
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- Klotho's impact on diabetic nephropathy and its emerging connection to diabetic retinopathy.Frontiers in endocrinology · 2023Review
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- TP63 Is Significantly Upregulated in Diabetic Kidney.International journal of molecular sciences · 2021Article
- PCR Array Technology in Biopsy Samples Identifies Up-Regulated mTOR Pathway Genes as Potential Rejection Biomarkers After Kidney Transplantation.Frontiers in medicine · 2021Article
- CSF-1 in Osteocytes Inhibits Nox4-mediated Oxidative Stress and Promotes Normal Bone Homeostasis.JBMR plus · 2020Article
- The tubular hypothesis of nephron filtration and diabetic kidney disease.Nature reviews. Nephrology · 2020Review
- Blockade of the mTOR signaling pathway with rapamycin ameliorates aristolochic acid nephropathy.Experimental and therapeutic medicine · 2020Article
- Podocyte Lysosome Dysfunction in Chronic Glomerular Diseases.International journal of molecular sciences · 2020Review
- SPAG5-AS1 inhibited autophagy and aggravated apoptosis of podocytes via SPAG5/AKT/mTOR pathway.Cell proliferation · 2020Article
- SGLT2 Inhibitors: Emerging Roles in the Protection Against Cardiovascular and Kidney Disease Among Diabetic Patients.International journal of nephrology and renovascular disease · 2020Review
- Proximal Tubule Autophagy Differs in Type 1 and 2 Diabetes.Journal of the American Society of Nephrology : JASN · 2019Article
- Galectin-1 is a new fibrosis protein in type 1 and type 2 diabetes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Preclinical evidence of the enhanced effectiveness of combined rapamycin and AICAR in reducing kidney cancer.Molecular oncology · 2018Article
- A new drug combination significantly reduces kidney tumor progression in kidney mouse model.Oncotarget · 2018Article
- Autophagy in diabetic kidney disease: regulation, pathological role and therapeutic potential.Cellular and molecular life sciences : CMLS · 2018Review
- Effect of Puerarin Regulated mTOR Signaling Pathway in Experimental Liver Injury.Frontiers in pharmacology · 2018Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Apoptosis contributes to the development of diabetic nephropathy, but the mechanism by which high glucose (HG) induces apoptosis is not fully understood. Because the tuberin/mTOR pathway can modulate apoptosis, we studied the role of this pathway in apoptosis in type I diabetes and in cultured proximal tubular epithelial (PTE) cells exposed to HG. Compared with control rats, diabetic rats had more apoptotic cells in the kidney cortex. Induction of diabetes also increased phosphorylation of tuberin in association with mTOR activation (measured by p70S6K phosphorylation), inactivation of Bcl-2, increased cytosolic cytochrome c expression, activation of caspase 3, and cleavage of PARP; insulin treatment prevented these changes. In vitro, exposure of PTE cells to HG increased phosphorylation of tuberin and p70S6K, phosphorylation of Bcl-2, expression of cytosolic cytochrome c, and caspase 3 activity. High glucose induced translocation of the caspase substrate YY1 from the cytoplasm to the nucleus and enhanced cleavage of PARP. Pretreatment the cells with the mTOR inhibitor rapamycin reduced the number of apoptotic cells induced by HG and the downstream effects of mTOR activation noted above. Furthermore, gene silencing of tuberin with siRNA decreased cleavage of PARP. These data show that the tuberin/mTOR pathway promotes apoptosis of tubular epithelial cells in diabetes, mediated in part by cleavage of PARP by YY1.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.