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Mycophenolate mofetil ameliorates diabetic nephropathy through epithelial mesenchymal transition in rats

  • Authors:
    • Xiaoyan Xiao
    • Jie Wang
    • Xiangdi Chang
    • Junhui Zhen
    • Gengyin Zhou
    • Zhao Hu
  • View Affiliations / Copyright

    Affiliations: Department of Nephrology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Pathology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
    Copyright: © Xiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 4043-4050
    |
    Published online on: June 15, 2015
       https://doi.org/10.3892/mmr.2015.3934
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Abstract

Recent studies in animal models have revealed that mycophenolate mofetil (MMF) has certain protective effects against experimental diabetic nephropathy. The present study therefore aimed to investigate the hypothesis that diabetic nephropathy may be ameliorated by mycophenolate mofetil and benazepril treatment alone or in combination, and identify the potential underlying mechanisms in a rat model. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin. Rats were subsequently treated with benazepril, MMF or a combination of the two drugs, and blood glucose, normalized kidney weight, urine protein and serum creatinine were determined. The pathological changes in renal tissue were also observed. In addition, indices of epithelial mesenchymal transition, including α‑smooth muscle actin (α‑SMA) and transforming growth factor (TGF)‑β1 expression, were examined. Normalized kidney weight, urine protein and serum creatinine levels were significantly improved in the diabetic rats treated with benazepril or mycophenolate mofetil, compared with those of rats in the untreated diabetic group. Pathological changes in the kidney were detected concurrently with increasing kidney weight and urinary albumin excretion, with a similar trend in variation among groups. In addition, the expression of epithelial mesenchymal transition indices, including α‑SMA and TGF‑β1, in the renal tubule interstitium were significantly decreased in the benazepril‑ and MMF‑treated groups compared with those of the diabetic group. As expected, the aforementioned indices were markedly lower in the benazepril and MMF combined treatment group than those in the single medication groups. These data suggested that MMF may have a protective role in diabetic nephropathy, and that the underlying mechanism may be partially dependent upon the suppression of the epithelial mesenchymal transition. Furthermore, the combination of benazepril and MMF conferred enhanced efficacy over monotherapies in the treatment of diabetic nephropathy.
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View References

1 

Ziyadeh FN and Sharma K: Overview: combating diabetic nephropathy. J Am Soc Nephrol. 14:1355–1357. 2003. View Article : Google Scholar : PubMed/NCBI

2 

Anil Kumar P, Welsh GI, Saleem MA and Menon RK: Molecular and cellular events mediating glomerular podocyte dysfunction and depletion in diabetes mellitus. Front Endocrinol (Lausanne). 5:1512014.

3 

Lan HY: Tubular epithelial-myofibroblast transdifferentiation mechanisms in proximal tubule cells. Curr Opin Nephrol Hypertens. 12:25–29. 2003. View Article : Google Scholar

4 

Loeffler I, Liebisch M and Wolf G: Collagen VIII influences epithelial phenotypic changes in experimental diabetic nephropathy. Am J Physiol Renal Physiol. 303:F733–F745. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Hills CE and Squires PE: TGF-beta1-induced epithelial-to-mesenchymal transition and therapeutic intervention in diabetic nephropathy. Am J Nephrol. 31:68–74. 2010. View Article : Google Scholar

6 

Hills CE and Squires PE: The role of TGF-β and epithelial-to mesenchymal transition in diabetic nephropathy. Cytokine Growth Factor Rev. 22:131–139. 2011.PubMed/NCBI

7 

Hills CE, Siamantouras E, Smith SW, Cockwell P, Liu KK and Squires PE: TGFβ modulates cell-to-cell communication in early epithelial-to-mesenchymal transition. Diabetologia. 55:812–824. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Wu YG, Lin H, Qian H, et al: Renoprotective effects of combination of angiotensin converting enzyme inhibitor with mycophenolate mofetil in diabetic rats. Inflamm Res. 55:192–199. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Utimura R, Fujihara CK, Mattar AL, Malheiros DM, Noronha IL and Zatz R: Mycophenolate mofetil prevents the development of glomerular injury in experimental diabetes. Kidney Int. 63:209–216. 2003. View Article : Google Scholar

10 

Fujihara CK, Noronha IL, Malheiros, Antunes GR, de Oliveira IB and Zatz R: Combined mycophenolate mofetil and losartan therapy arrests established injury in the remnant kidney. J Am Soc Nephrol. 11:283–290. 2000.PubMed/NCBI

11 

Wesson DE, Nathan T, Rose T, Simoni J and Tran RM: Dietary protein induces endothelin-mediated kidney injury through enhanced intrinsic acid production. Kidney Int. 71:210–217. 2007. View Article : Google Scholar

12 

Marquez B, Zouvani I, Karagrigoriou A, Anastasiades E, Pierides A and Kyriacou K: A simplified method for measuring the thickness of glomerular basement membranes. Ultrastruct Pathol. 27:409–416. 2003. View Article : Google Scholar : PubMed/NCBI

13 

Najafian B, Alpers CE and Fogo AB: Pathology of human diabetic nephropathy. Contrib Nephrol. 170:36–47. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Bonventre JV: Can we target tubular damage to prevent renal function decline in diabetes? Semin Nephrol. 32:452–462. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Habib SL: Alterations in tubular epithelial cells in diabetic nephropathy. J Nephrol. 26:865–869. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Liu Y: Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance, molecular mechanism, and therapeutic intervention. J Am Soc Nephrol. 15:1–12. 2004. View Article : Google Scholar

17 

Wilkins-Port CE and Higgins PJ: Regulation of extracellular matrix remodeling following transforming growth factor-beta1/epidermal growth factor-stimulated epithelial-mesenchymal transition in human premalignant keratinocytes. Cells Tissues Organs. 185:116–122. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Hills CE and Squires PE: The role of TGF-β and epithelial-to mesenchymal transition in diabetic nephropathy. Cytokine Growth Factor Rev. 22:131–139. 2011.PubMed/NCBI

19 

Ina K, Kitamura H, Tatsukawa S and Fujikura Y: Significance of α-SMA in myofibroblasts emerging in renal tubulointerstitial fibrosis. Histol Histopathol. 26:855–866. 2011.PubMed/NCBI

20 

Tylicki L, Lizakowski S and Rutkowski B: Renin-angiotensin-aldosterone system blockade for nephroprotection: current evidence and future directions. J Nephrol. 25:900–910. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Wolf G: Renal injury due to renin-angiotensin-aldosterone system activation of the transforming growth factor-beta pathway. Kidney Int. 70:1914–1919. 2006.PubMed/NCBI

22 

Esteban V, Lorenzo O, Rupérez M, et al: Angiotensin II, via AT1 and AT2 receptors and NF-kappaB pathway, regulates the inflammatory response in unilateral ureteral obstruction. J Am Soc Nephrol. 15:1514–1529. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Allison AC: Mechanisms of action of mycophenolate mofetil. Lupus. 14(Suppl 1): s2–s8. 2005. View Article : Google Scholar : PubMed/NCBI

24 

Roos N, Poulalhon N, Farge D, Madelaine I, Mauviel A and Verrecchia F: In vitro evidence for a direct antifibrotic role of the immunosuppressive drug mycophenolate mofetil. J Pharmacol Exp Ther. 321:583–589. 2007. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Xiao X, Wang J, Chang X, Zhen J, Zhou G and Hu Z: Mycophenolate mofetil ameliorates diabetic nephropathy through epithelial mesenchymal transition in rats. Mol Med Rep 12: 4043-4050, 2015.
APA
Xiao, X., Wang, J., Chang, X., Zhen, J., Zhou, G., & Hu, Z. (2015). Mycophenolate mofetil ameliorates diabetic nephropathy through epithelial mesenchymal transition in rats. Molecular Medicine Reports, 12, 4043-4050. https://doi.org/10.3892/mmr.2015.3934
MLA
Xiao, X., Wang, J., Chang, X., Zhen, J., Zhou, G., Hu, Z."Mycophenolate mofetil ameliorates diabetic nephropathy through epithelial mesenchymal transition in rats". Molecular Medicine Reports 12.3 (2015): 4043-4050.
Chicago
Xiao, X., Wang, J., Chang, X., Zhen, J., Zhou, G., Hu, Z."Mycophenolate mofetil ameliorates diabetic nephropathy through epithelial mesenchymal transition in rats". Molecular Medicine Reports 12, no. 3 (2015): 4043-4050. https://doi.org/10.3892/mmr.2015.3934
Copy and paste a formatted citation
x
Spandidos Publications style
Xiao X, Wang J, Chang X, Zhen J, Zhou G and Hu Z: Mycophenolate mofetil ameliorates diabetic nephropathy through epithelial mesenchymal transition in rats. Mol Med Rep 12: 4043-4050, 2015.
APA
Xiao, X., Wang, J., Chang, X., Zhen, J., Zhou, G., & Hu, Z. (2015). Mycophenolate mofetil ameliorates diabetic nephropathy through epithelial mesenchymal transition in rats. Molecular Medicine Reports, 12, 4043-4050. https://doi.org/10.3892/mmr.2015.3934
MLA
Xiao, X., Wang, J., Chang, X., Zhen, J., Zhou, G., Hu, Z."Mycophenolate mofetil ameliorates diabetic nephropathy through epithelial mesenchymal transition in rats". Molecular Medicine Reports 12.3 (2015): 4043-4050.
Chicago
Xiao, X., Wang, J., Chang, X., Zhen, J., Zhou, G., Hu, Z."Mycophenolate mofetil ameliorates diabetic nephropathy through epithelial mesenchymal transition in rats". Molecular Medicine Reports 12, no. 3 (2015): 4043-4050. https://doi.org/10.3892/mmr.2015.3934
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