Effect of astragalus injection on renal tubular epithelial transdifferentiation in type 2 diabetic mice.

BACKGROUND: Astragalus injection is used by practitioners of traditional Chinese medicine to treat diabetic nephropathy (DN). The current study was conducted to determine the effect of astragalus on tubular epithelial transdifferentiation during the progression of DN in KKAy mice, as well as to investigate the molecular mechanism underlying this effect. METHODS: Diabetic, 14-week-old, male KKAy mice were randomly divided into a model group and an astragalus treatment group, while age-matched male C57BL/6 J mice were selected as controls. The treatment group received daily intraperitoneal injections of astragalus (0.03 mL/10 g per day), while the model group received injections of an equal volume of saline. Mice were euthanized after 24 weeks. Serum samples were obtained from the animals in each group for blood glucose measurement. Kidney tissue samples were used for morphometric studies. The mRNA and protein expression levels of transforming growth factor beta 1 (TGF-ß1), transforming growth factor beta receptor 1 (TGFß-R1), alpha smooth muscle actin (α-SMA), and E-cadherin were evaluated using real-time polymerase chain reaction (PCR) and western blotting. RESULTS: Astragalus significantly reduced blood glucose levels; inhibited morphological changes in the kidneys of KKAy mice; reduced mRNA and protein expression levels of TGF-ß1, TGFß-R1, and α-SMA; and increased E-cadherin expression. CONCLUSIONS: Tubular epithelial transdifferentiation plays an important role in the development of DN in diabetic mice. Administration of astragalus likely prevents or mitigates DN by suppressing tubular epithelial transdifferentiation, protecting KKAy mice from renal damage.

Effects of astragalus injection on the TGFß/Smad pathway in the kidney in type 2 diabetic mice.

BACKGROUND: In traditional Chinese medicine, astragalus injection is used to treat diabetic nephropathy (DN). The current study was conducted to determine the effects of astragalus injection on DN by assessing potential modulation of the transforming growth factor beta TGFß/Smad signaling pathway. METHODS: Diabetic, male KKAy mice, aged 14 weeks were randomly divided into a model group and an astragalus treatment group, while age-matched male C57BL/6J mice were selected as controls. The treatment group received daily intraperitoneal injections of astragalus (0.03 ml/10 g.d), while the model group received injections of an equivalent volume of saline. Mice were euthanized after 24 weeks. Serum samples were obtained from animals in each group, and blood glucose, creatinine, and urea nitrogen levels were measured. Tissue samples from the kidney were used for morphometric studies. The expression of TGFß1, TGFßR-Ι, Smad3, and Smad7 were evaluated using reverse transcription-polymerase chain reaction (RT-PCR), and western blot analysis. RESULTS: Mice in the model group became obese, and suffered complications, including hyperglycemia, polyuria, and proteinuria. Astragalus treatment significantly reduced albuminuria, improved renal function, and ameliorated changes in renal histopathology. Moreover, administration of astragalus injection increased Smad7 expression, and inhibited the expression of TGFßR-Ι, Smad3 and its phosphorylation, and decreased the mRNA level of TGFß1. CONCLUSIONS: The TGFß/Smad signaling pathway plays an important role in the development of DN. Administration of astragalus injection could prevent or mitigate DN by rebalancing TGFß/Smad signaling, and could play a protective role in DN-induced renal damage in KKAy mice.