PloS one, 2016-03, Vol.11 (3), p.e0151857-e0151857
2016
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- Autor(en) / Beteiligte
- Titel
- Amelioration of Diabetic Mouse Nephropathy by Catalpol Correlates with Down-Regulation of Grb10 Expression and Activation of Insulin-Like Growth Factor 1 / Insulin-Like Growth Factor 1 Receptor Signaling
- Ist Teil von
- PloS one, 2016-03, Vol.11 (3), p.e0151857-e0151857
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2016
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Growth factor receptor-bound protein 10 (Grb10) is an adaptor protein that can negatively regulate the insulin-like growth factor 1 receptor (IGF-1R). The IGF1-1R pathway is critical for cell growth and apoptosis and has been implicated in kidney diseases; however, it is still unknown whether Grb10 expression is up-regulated and plays a role in diabetic nephropathy. Catalpol, a major active ingredient of a traditional Chinese medicine, Rehmannia, has been reported to possess anti-inflammatory and anti-aging activities and then used to treat diabetes. Herein, we aimed to assess the therapeutic effect of catalpol on a mouse model diabetic nephropathy and the potential role of Grb10 in the pathogenesis of this diabetes-associated complication. Our results showed that catalpol treatment improved diabetes-associated impaired renal functions and ameliorated pathological changes in kidneys of diabetic mice. We also found that Grb10 expression was significantly elevated in kidneys of diabetic mice as compared with that in non-diabetic mice, while treatment with catalpol significantly abrogated the elevated Grb10 expression in diabetic kidneys. On the contrary, IGF-1 mRNA levels and IGF-1R phosphorylation were significantly higher in kidneys of catalpol-treated diabetic mice than those in non-treated diabetic mice. Our results suggest that elevated Grb10 expression may play an important role in the pathogenesis of diabetic nephropathy through suppressing IGF-1/IGF-1R signaling pathway, which might be a potential molecular target of catalpol for the treatment of this diabetic complication.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0151857Titel-ID: cdi_plos_journals_1774172829
- Format
- –
- Schlagworte
- Aging, Analysis, Animals, Apoptosis, Biology and Life Sciences, Blotting, Western, Diabetes mellitus, Diabetes Mellitus, Experimental - complications, Diabetic nephropathies, Diabetic Nephropathies - drug therapy, Diabetic Nephropathies - metabolism, Diabetic Nephropathies - physiopathology, Diabetic nephropathy, Disease Models, Animal, Down-regulation, Down-Regulation - drug effects, Drugs, Chinese Herbal - pharmacology, Drugs, Chinese Herbal - therapeutic use, Gene expression, Gene Expression - drug effects, Gene Expression - physiology, Glucose, GRB10 Adaptor Protein - biosynthesis, GRB10 Adaptor Protein - physiology, Hypoglycemic Agents - pharmacology, Hypoglycemic Agents - therapeutic use, Inflammation, Insulin, Insulin-like growth factor I, Insulin-Like Growth Factor I - metabolism, Insulin-Like Growth Factor I - physiology, Insulin-like growth factors, Iridoid Glucosides - pharmacology, Iridoid Glucosides - therapeutic use, Kidney - drug effects, Kidney - metabolism, Kidney - physiopathology, Kidney diseases, Kidneys, Kinases, Male, Medicine and Health Sciences, Mice, Mice, Inbred C57BL, mRNA, Nephropathy, Pathogenesis, Phosphorylation, Physical Sciences, Polymerase Chain Reaction, Receptor, IGF Type 1 - metabolism, Receptor, IGF Type 1 - physiology, Research and Analysis Methods, Risk factors, Rodents, Signal transduction, Signaling, Traditional Chinese medicine