PTEN-induced kinase 1 deficiency alters albumin permeability and insulin signaling in podocytes
| العنوان: | PTEN-induced kinase 1 deficiency alters albumin permeability and insulin signaling in podocytes |
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| المؤلفون: | Irena Audzeyenka, Patrycja Rachubik, Marlena Typiak, Tomasz Kulesza, Daria Kalkowska, Dorota Rogacka, Michał Rychłowski, Stefan Angielski, Moin Saleem, Agnieszka Piwkowska |
| المصدر: | Journal of Molecular Medicine. 100:903-915 |
| بيانات النشر: | Springer Science and Business Media LLC, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Podocytes, PTEN Phosphohydrolase, Permeability, Glucose, Albumins, Hyperglycemia, Drug Discovery, Humans, Insulin, Molecular Medicine, Diabetic Nephropathies, Protein Kinases, Genetics (clinical), Signal Transduction |
| الوصف: | Alterations of insulin signaling in diabetes are associated with podocyte injury, proteinuria, and renal failure. Insulin stimulates glucose transport to cells and regulates other intracellular processes that are linked to cellular bioenergetics, such as autophagy, gluconeogenesis, fatty acid metabolism, and mitochondrial homeostasis. The dysfunction of mitochondrial dynamics, including mitochondrial fusion, fission, and mitophagy, has been observed in high glucose-treated podocytes and renal cells from patients with diabetes. Previous studies showed that prolonged hyperglycemia is associated with the development of insulin resistance in podocytes, and high glucose-treated podocytes exhibit an increase in mitochondrial fission and decrease in markers of mitophagy. In the present study, we found that deficiency of the main mitophagy protein PTEN-induced kinase 1 (PINK1) significantly increased albumin permeability and hampered glucose uptake to podocytes. We suggest that PINK1 inhibition impairs the insulin signaling pathway, in which lower levels of phosphorylated Akt and membrane fractions of the insulin receptor and glucose transporter-4 were observed. Moreover, PINK1-depleted podocytes exhibited lower podocin and nephrin expression, thus identifying a potential mechanism whereby albumin leakage increases under hyperglycemic conditions when mitophagy is inhibited. In conclusion, we found that PINK1 plays an essential role in insulin signaling and the maintenance of proper permeability in podocytes. Therefore, PINK1 may be a potential therapeutic target for the treatment or prevention of diabetic nephropathy. |
| تدمد: | 1432-1440 0946-2716 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::84521cc634c02cbb4a3b76337aa43f0aTest https://doi.org/10.1007/s00109-022-02204-4Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....84521cc634c02cbb4a3b76337aa43f0a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14321440 09462716 |
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