Abstract
BackgroundAstragalus 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.MethodsDiabetic, 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-β1), transforming growth factor beta receptor 1 (TGFβ-R1), alpha smooth muscle actin (α-SMA), and E-cadherin were evaluated using real-time polymerase chain reaction (PCR) and western blotting.ResultsAstragalus significantly reduced blood glucose levels; inhibited morphological changes in the kidneys of KKAy mice; reduced mRNA and protein expression levels of TGF-β1, TGFβ-R1, and α-SMA; and increased E-cadherin expression.ConclusionsTubular 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.
Highlights
Astragalus injection is used by practitioners of traditional Chinese medicine to treat diabetic nephropathy (DN)
The major pathological change associated with DN is renal interstitial fibrosis (RIF), which is characterized by renal tubular atrophy and accumulation of extracellular matrix components (ECM) in the renal glomeruli and interstitium
Astragalus administration controls blood glucose levels No apparent fluctuations in behaviour or physiological appearance were noted among mice in the control group
Summary
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. Transdifferentiation of tubular epithelial cells to myofibroblast-like cells has been proposed as the central link in the development of RIF [2, 3]. Transforming growth factor beta 1 (TGF-β1) is recognized as the most important cytokine in the induction of epithelial transdifferentiation [4, 5]. TGF-β1 binds to transforming growth factor beta receptor 1 (TGFβ-R1) and inhibits the expression of E-cadherin, an epithelial cell adhesion molecule, resulting in shedding of epithelial cells from the basement membrane [6, 7]. TGF-β1 can upregulate the expression of alpha smooth muscle actin (α-SMA), which can stimulate the production of myofibroblast-like cells [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
