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Published in: BMC Complementary Medicine and Therapies 1/2016

Open Access 01-12-2016 | Research article

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

Authors: Yue-e Yi, Shu-yu Li, Yan-na Nie, De-xian Jia, Zhi-hui Zhang, Yan-fei Wang, Qian Wang

Published in: BMC Complementary Medicine and Therapies | Issue 1/2016

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Abstract

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-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.

Results

Astragalus 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.

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.
Literature
1.
go back to reference Wu AY, Kong NC, de Leon FA, et al. An alarmingly high prevalence of diabetic nephropathy in Asian type 2 diabetic patients: the Microalbuminuria Prevalence (MAP) Study. Diabetologia. 2005;48(1):17–26.CrossRefPubMed Wu AY, Kong NC, de Leon FA, et al. An alarmingly high prevalence of diabetic nephropathy in Asian type 2 diabetic patients: the Microalbuminuria Prevalence (MAP) Study. Diabetologia. 2005;48(1):17–26.CrossRefPubMed
2.
go back to reference Du F, Li S, Wang T, Zhang HY, et al. Implication of Bcl-2-associated athanogene 3 in fibroblast growth factor-2-mediated epithelial-mesenchymal transition in renal epithelial cells. Exp Biol Med (Maywood). 2015;240(5):566–75.CrossRef Du F, Li S, Wang T, Zhang HY, et al. Implication of Bcl-2-associated athanogene 3 in fibroblast growth factor-2-mediated epithelial-mesenchymal transition in renal epithelial cells. Exp Biol Med (Maywood). 2015;240(5):566–75.CrossRef
3.
go back to reference He L, Lou W, Ji L, Liang W, Zhou M, et al. Serum Response Factor Accelerates the High Glucose-Induced Epithelial-to-Mesenchymal Transition (EMT) via Snail Signaling in Human Peritoneal Mesothelial Cells. PLoS One. 2014;9(10):e108593.CrossRefPubMedPubMedCentral He L, Lou W, Ji L, Liang W, Zhou M, et al. Serum Response Factor Accelerates the High Glucose-Induced Epithelial-to-Mesenchymal Transition (EMT) via Snail Signaling in Human Peritoneal Mesothelial Cells. PLoS One. 2014;9(10):e108593.CrossRefPubMedPubMedCentral
4.
go back to reference Docherty NG. O, sullivan OE, et al. TGF-β1 Induced EMT Can Occur Independently of its Proapoptotic Effects And Is Aided By EGF Receptor Activation. Am J Physiol Renal. 2006;290(5):F1202–12.CrossRef Docherty NG. O, sullivan OE, et al. TGF-β1 Induced EMT Can Occur Independently of its Proapoptotic Effects And Is Aided By EGF Receptor Activation. Am J Physiol Renal. 2006;290(5):F1202–12.CrossRef
5.
go back to reference Strutz F, Zeisberg M, et al. Role of basic fibroblast growth factor in epithelial-mesenchymal transformation. J Kidney Int. 2002;61(5):1714–28.CrossRef Strutz F, Zeisberg M, et al. Role of basic fibroblast growth factor in epithelial-mesenchymal transformation. J Kidney Int. 2002;61(5):1714–28.CrossRef
6.
go back to reference Yang J, Liu Y. Dissection of key events in tubular epithelial to myofibroblast transition and its implications in renal interstitial fibrosis. Am J Pathology. 2001;159(4):1465–75.CrossRef Yang J, Liu Y. Dissection of key events in tubular epithelial to myofibroblast transition and its implications in renal interstitial fibrosis. Am J Pathology. 2001;159(4):1465–75.CrossRef
7.
go back to reference Zeisberg M, Hanai J, et al. BMP-7 counteracts TGF-1-induced EMT and reverses chronic renal injury. Nat Med. 2003;9(7):964–8.CrossRefPubMed Zeisberg M, Hanai J, et al. BMP-7 counteracts TGF-1-induced EMT and reverses chronic renal injury. Nat Med. 2003;9(7):964–8.CrossRefPubMed
8.
go back to reference Moon YM, Park IH, Cho JS, et al. Berberine inhibits myofibroblast differentiation in nasal polyp-derived fibroblasts via the p38 pathway. Phytother Res. 2013;27(1):16–20.CrossRefPubMed Moon YM, Park IH, Cho JS, et al. Berberine inhibits myofibroblast differentiation in nasal polyp-derived fibroblasts via the p38 pathway. Phytother Res. 2013;27(1):16–20.CrossRefPubMed
9.
go back to reference Xie W, Zhao Y, Zhang Y. Traditional Chinese medicines in treatment of patients with type 2 diabetes mellitus. Evid Based Complement Altern Med. 2011;2011:726–3. Xie W, Zhao Y, Zhang Y. Traditional Chinese medicines in treatment of patients with type 2 diabetes mellitus. Evid Based Complement Altern Med. 2011;2011:726–3.
10.
go back to reference Jin M, Zhao K, Huang Q, Shang P. Structural features and biological activities of the polysaccharides from Astragalus membranaceus. Int J Biol Macromol. 2014;64:257–66.CrossRefPubMed Jin M, Zhao K, Huang Q, Shang P. Structural features and biological activities of the polysaccharides from Astragalus membranaceus. Int J Biol Macromol. 2014;64:257–66.CrossRefPubMed
11.
go back to reference Kim J, Moon E, Kwon S. Effect of Astragalus membranaceus extract on diabetic nephropathy. Endocrine Diabetes Metab Case Rep. 2014;2014:140063. Kim J, Moon E, Kwon S. Effect of Astragalus membranaceus extract on diabetic nephropathy. Endocrine Diabetes Metab Case Rep. 2014;2014:140063.
12.
go back to reference Wang HY. Antifibrotic effect of the Chinese herbs Astragalus mongholicus and Angelica sinensis, in a rat model of chronic puromycin aminonucleoside nephrosis. Life Sci. 2004;74:1645–58.CrossRefPubMed Wang HY. Antifibrotic effect of the Chinese herbs Astragalus mongholicus and Angelica sinensis, in a rat model of chronic puromycin aminonucleoside nephrosis. Life Sci. 2004;74:1645–58.CrossRefPubMed
13.
go back to reference Li Y, Lai Y, Li S, Wu Y, Wang Q. Influence of huangqi injection on tubular epithelial-mesenchymal transition. J Beijing Univ Tradit Chin Med. 2012;35(2):109–16. Li Y, Lai Y, Li S, Wu Y, Wang Q. Influence of huangqi injection on tubular epithelial-mesenchymal transition. J Beijing Univ Tradit Chin Med. 2012;35(2):109–16.
14.
go back to reference Mason RM, Wahab NA. Extracellular matrix metabolism in diabetic nephropathy. J Am Soc Nephrol. 2003;14:1358–73.CrossRefPubMed Mason RM, Wahab NA. Extracellular matrix metabolism in diabetic nephropathy. J Am Soc Nephrol. 2003;14:1358–73.CrossRefPubMed
15.
go back to reference Schena FP, Gesualdo L. Pathogenetic mechanisms of diabetic nephropathy. J Am Soc Nephrol. 2005;16:30–3.CrossRef Schena FP, Gesualdo L. Pathogenetic mechanisms of diabetic nephropathy. J Am Soc Nephrol. 2005;16:30–3.CrossRef
16.
go back to reference Tomino Y. Lessons from the KKAy Mouse, a spontaneous animal model for the treatment of human type 2 diabetic nephropathy. Nephro-Urol Mon. 2011;4:524–5.CrossRef Tomino Y. Lessons from the KKAy Mouse, a spontaneous animal model for the treatment of human type 2 diabetic nephropathy. Nephro-Urol Mon. 2011;4:524–5.CrossRef
17.
go back to reference Li M, Wang W, Xue J, Gu Y, Lin S. Meta-analysis of the clinical value of astragalus membranaceus in diabetic nephropathy. J Ethnopharmacol. 2011;133:412–9.CrossRefPubMed Li M, Wang W, Xue J, Gu Y, Lin S. Meta-analysis of the clinical value of astragalus membranaceus in diabetic nephropathy. J Ethnopharmacol. 2011;133:412–9.CrossRefPubMed
18.
go back to reference Zhang J, Xie X, Li C, Fu P. Systematic review of the renal protective effect of Astragalus (root) on diabetic nephropathy in animal models. J Ethnopharmacol. 2009;126:189–96.CrossRefPubMed Zhang J, Xie X, Li C, Fu P. Systematic review of the renal protective effect of Astragalus (root) on diabetic nephropathy in animal models. J Ethnopharmacol. 2009;126:189–96.CrossRefPubMed
19.
go back to reference Liao WP, Shi YG. Effect of astragalus polysaccharides and soy isoflavones on glucose metabolism in diabetic rats. Acta Acad Med Militaris Tertiae. 2007;29:416–8. Liao WP, Shi YG. Effect of astragalus polysaccharides and soy isoflavones on glucose metabolism in diabetic rats. Acta Acad Med Militaris Tertiae. 2007;29:416–8.
20.
go back to reference Zhou F, Mao XQ, Wang N, Liu J, Ou-Yang JP. Astragalus polysaccharides alleviates glucose toxicity and restores glucose homeostasis in diabetic states via activation of AMPK. Acta Pharmacol Sin. 2009;30:1607–15.CrossRef Zhou F, Mao XQ, Wang N, Liu J, Ou-Yang JP. Astragalus polysaccharides alleviates glucose toxicity and restores glucose homeostasis in diabetic states via activation of AMPK. Acta Pharmacol Sin. 2009;30:1607–15.CrossRef
21.
go back to reference Liu M, Qin J, Hao Y, Liu M, Luo J, Luo T, Wei L. Astragalus polysaccharide suppresses skeletal muscle myostatin expression in diabetes: involvement of ROS-ERK and NF-kB pathways. Oxid Med Cell Longev. 2013;2013:782497.PubMedPubMedCentral Liu M, Qin J, Hao Y, Liu M, Luo J, Luo T, Wei L. Astragalus polysaccharide suppresses skeletal muscle myostatin expression in diabetes: involvement of ROS-ERK and NF-kB pathways. Oxid Med Cell Longev. 2013;2013:782497.PubMedPubMedCentral
22.
go back to reference Ye Y, Deng T, Wan XY, Ouyang JP, Liu M, Mao XQ. The role of quantitative changes in the epxression of insulin receptor substrate-1 and nuclear ubiquitin in abnormal glycometabolism in the livers of KKAy mice and the relative therapeutic mechanisms of Astragalus polysaccharide. Int J Mol Med. 2014;33(2):341–50.PubMed Ye Y, Deng T, Wan XY, Ouyang JP, Liu M, Mao XQ. The role of quantitative changes in the epxression of insulin receptor substrate-1 and nuclear ubiquitin in abnormal glycometabolism in the livers of KKAy mice and the relative therapeutic mechanisms of Astragalus polysaccharide. Int J Mol Med. 2014;33(2):341–50.PubMed
23.
go back to reference Xiao M, Li H, Xie X. Astragalus Mongholicus may regulate rat renal tubular cell transdifferrentiation induced by TGF-β1 through C- met dependent pathway. Chin J Integr Tradit West Nephrol. 2008;9:764–8. Xiao M, Li H, Xie X. Astragalus Mongholicus may regulate rat renal tubular cell transdifferrentiation induced by TGF-β1 through C- met dependent pathway. Chin J Integr Tradit West Nephrol. 2008;9:764–8.
24.
go back to reference Fanb JM, N YY. Transforming growth factor-β1 reulates tubular epithelium of fibroblast transdifferentitation in vivo. Kidney Int. 1999;56(4):1455–67.CrossRef Fanb JM, N YY. Transforming growth factor-β1 reulates tubular epithelium of fibroblast transdifferentitation in vivo. Kidney Int. 1999;56(4):1455–67.CrossRef
25.
go back to reference Kawai T, Masaki T, Doi S. PPAR · gamma agonist attenuates renal interstitial fibrosis and inflammation through reduction of TGFbeta[J]. Lab Invest. 2009;89(1):47–58.CrossRefPubMed Kawai T, Masaki T, Doi S. PPAR · gamma agonist attenuates renal interstitial fibrosis and inflammation through reduction of TGFbeta[J]. Lab Invest. 2009;89(1):47–58.CrossRefPubMed
26.
go back to reference Jinde K, Nikolic-Paterson DJ, et al. Tubular phenotypic change inprogressive tubulointerstit-ial Fibrosis in human glomerulonephritis. Am J Kidney Dis. 2001;38:761–9.CrossRefPubMed Jinde K, Nikolic-Paterson DJ, et al. Tubular phenotypic change inprogressive tubulointerstit-ial Fibrosis in human glomerulonephritis. Am J Kidney Dis. 2001;38:761–9.CrossRefPubMed
27.
go back to reference Li L, Emmett N, Mann D, Zhao X. Fenofibrate attenuates tubulointerstitial fibrosis and inflammation through suppression of nuclear factor-kB and transforming growth factor-β1/Smad3 in diabetic nephropathy. Exp Biol Med. 2010;235:383–91.CrossRef Li L, Emmett N, Mann D, Zhao X. Fenofibrate attenuates tubulointerstitial fibrosis and inflammation through suppression of nuclear factor-kB and transforming growth factor-β1/Smad3 in diabetic nephropathy. Exp Biol Med. 2010;235:383–91.CrossRef
28.
go back to reference Steinberg MS, McNutt PM. Cadherin and their connections:adhesion junctions have broader functions. Curr Opin Cell Biol. 1999;11:554–60.CrossRefPubMed Steinberg MS, McNutt PM. Cadherin and their connections:adhesion junctions have broader functions. Curr Opin Cell Biol. 1999;11:554–60.CrossRefPubMed
29.
go back to reference Bush KT, Tsukamoto T, et al. Selective degradation of E-cadherin and dissolution of E-cadherin-catenin complexes in epithelial is chemia. Am J Physiol. 2000;278:F847–52. Bush KT, Tsukamoto T, et al. Selective degradation of E-cadherin and dissolution of E-cadherin-catenin complexes in epithelial is chemia. Am J Physiol. 2000;278:F847–52.
30.
go back to reference Gloushankova NA. Changes in regulation of cell- cell adhesion during tumor transformation[J]. Biochemistry (Mosc). 2008;7:742–50.CrossRef Gloushankova NA. Changes in regulation of cell- cell adhesion during tumor transformation[J]. Biochemistry (Mosc). 2008;7:742–50.CrossRef
31.
go back to reference Qi W, Chen X, Paronnik P, et al. The renal comical fibroblast in renal tubulointemtitial fibrosis[J]. Int J Biochem Cell Bid. 2006;38(1):1–5.CrossRef Qi W, Chen X, Paronnik P, et al. The renal comical fibroblast in renal tubulointemtitial fibrosis[J]. Int J Biochem Cell Bid. 2006;38(1):1–5.CrossRef
32.
go back to reference Sheng-bin XIE, Wei-ming WANG. Progression of renal tubulointerstitial fibrosis and expression of α-SMA,TGF-Bl and VDR in rat UU0 models. J of Shanghai Jiao Tong Univ (Med Sci). 2010;07:757–8. Sheng-bin XIE, Wei-ming WANG. Progression of renal tubulointerstitial fibrosis and expression of α-SMA,TGF-Bl and VDR in rat UU0 models. J of Shanghai Jiao Tong Univ (Med Sci). 2010;07:757–8.
33.
go back to reference Alexopoulos E, Gionanlis L, Papayianni E, et al. Predictors of outcome in idiopathic rapidly progressive glomerulonephritis(IRPGN)[J]. BMC Nephrol. 2006;7:16.CrossRefPubMedPubMedCentral Alexopoulos E, Gionanlis L, Papayianni E, et al. Predictors of outcome in idiopathic rapidly progressive glomerulonephritis(IRPGN)[J]. BMC Nephrol. 2006;7:16.CrossRefPubMedPubMedCentral
Metadata
Title
Effect of astragalus injection on renal tubular epithelial transdifferentiation in type 2 diabetic mice
Authors
Yue-e Yi
Shu-yu Li
Yan-na Nie
De-xian Jia
Zhi-hui Zhang
Yan-fei Wang
Qian Wang
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2016
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-016-1208-8

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