RESUMEN
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.
Asunto(s)
Nefropatías Diabéticas/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Proteína Adaptadora GRB10/fisiología , Hipoglucemiantes/uso terapéutico , Factor I del Crecimiento Similar a la Insulina/fisiología , Glucósidos Iridoides/uso terapéutico , Receptor IGF Tipo 1/fisiología , Animales , Western Blotting , Diabetes Mellitus Experimental/complicaciones , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/fisiopatología , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Proteína Adaptadora GRB10/biosíntesis , Expresión Génica/efectos de los fármacos , Expresión Génica/fisiología , Hipoglucemiantes/farmacología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Glucósidos Iridoides/farmacología , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , Reacción en Cadena de la Polimerasa , Receptor IGF Tipo 1/metabolismoRESUMEN
OBJECTIVE: To study the renal protective effect of sodium ferulate (SF) and its mechanism in rats with diabetic mellitus (DM). METHODS: DM rats induced by streptozotocin were treated with SF 110 mg/kg per day for 8 weeks. The ratio of kidney weight/body weight (KW/BW), serum triglyceride (TG) and total cholesterol (TC), creatinine clearance rate (Ccr), urinary protein/24 hrs, levels of endothelin-1 (ET-1) and nitric oxide (NO) in renal cortex in rats were measured, the pathological change of kidney were observed and the expression of transforming growth factor-beta 1 (TGF-beta 1) and collagen IV (C-IV) in kidney were examined using immunohistochemical assay. The data obtained were compared with those obtained from untreated DM rats and normal rats respectively. RESULTS: Compared with the normal rats, in DM rats, Ccr, urinary protein/24 hrs, ET-1, expressions of TGF-beta 1 and C-IV were significantly increased in DM model rats (all P < 0.01), and significantly abnormal pathological change in kidney was found. While in the SF treated DM rats, the above-mentioned abnormal changes were all significantly improved. CONCLUSION: SF has effect in protecting kidney of DM rats, the mechanism might be related with its actions of reducing ET-1 production in kidney and inhibiting the expressions of TGF-beta 1 and C-IV.