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Caffeic Acid Modulates miR-636 Expression in Diabetic Nephropathy Rats

Indian Journal of Clinical Biochemistry volume 34, pages 296–303 (2019)Cite this article

Abstract

We investigated the action of caffeic acid in regulating miR-636 expression level in kidney of streptozotocin-induced diabetic rats. Streptozotocin-induced diabetic rats were orally treated with caffeic acid at 40 mg/kg/day for 8 weeks. At the end of the treatment, body and kidney weight and blood glucose levels were determined, blood, urine, and kidneys were collected for biochemical and histological examination. Expression levels of miR-636 were determined in liver by qRT-PCR. Induction of diabetic nephropathy by streptozotocin was evidenced by displayed elevated levels of serum creatinine, blood urea nitrogen, microalbuminuria and urinary albumin/creatinine ratio in addition to renal hypotrophy. Caffeic acid (CA) can ameliorate renal damage and significantly decreased the fasting blood glucose, cholesterol and triglyceride in diabetic rats. CA treatment improved histological architecture in the diabetic kidney. CA significantly down regulate miR-636 expression level in the kidney of diabetic rats in comparison to healthy group. Overall, caffeic acid down regulates miR-636 expression level which is involved in development of diabetic nephropathy and might therefore be potential attractive therapeutic agent to pursue in DN.

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References

  1. Kato M, Natarajan R. Diabetic nephropathy—emerging epigenetic mechanisms. Nat Rev Nephrol. 2014;10:517–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Badal SS, Danesh FR. Diabetic nephropathy: emerging biomarkers for risk assessment. Diabetes. 2015;64:3063–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kume S, Koya D. Autophagy: a novel therapeutic target for diabetic nephropathy. Diabetes Metab J. 2015;39:451–60.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Yang Y, Liang C. MicroRNAs: an emerging player in autophagy. Science Open Res. 2015;2015. https://doi.org/10.14293/S2199-1006.1.

  5. Peng Y, Croce C. The role of MicroRNAs in human cancer. Signal Transduct Target Ther. 2016;1:15004.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Matboli M, Eissa S, Ibrahim D, Hegazy MGA, Imam SS, Habib EK. Caffeic acid attenuates diabetic kidney disease via modulation of autophagy in a high-fat diet/streptozotocin-induced diabetic rat. Sci Rep. 2017;7:2263.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Eissa S, Matboli M, Aboushahba R, Bekhet MM, Soliman Y. Urinary exosomal microRNA panel unravels novel biomarkers for diagnosis of type 2 diabetic kidney disease. J Diabetes Its Complic. 2016;30:1585–92.

    Article  Google Scholar 

  8. Lv M, Chen Z, Hu G, Li Q. Therapeutic strategies of diabetic nephropathy: recent progress and future perspectives. Drug Discov Today. 2015;20:332–46.

    Article  CAS  PubMed  Google Scholar 

  9. Dhungyal B, Koirala P, Sharma C, Jha DK. Caffeic acid—a potent phytocompound against diabetes mellitus a review. SMU Med J. 2014;1:152–60.

    Google Scholar 

  10. Yang N, Dang S, Shi J, Wu F, Li M, Zhang X, et al. Caffeic acid phenethyl ester attenuates liver fibrosis via inhibition of TGF-β1/Smad3 pathway and induction of autophagy pathway. Biochem Biophys Res Commun. 2017;486:22–8.

    Article  CAS  PubMed  Google Scholar 

  11. Sakata N, Yoshimatsu G, Tsuchiya H, Egawa S, Unno M. Animal models of diabetes mellitus for islet transplantation. Exp Diabetes Res. 2012;18:499–502.

    Google Scholar 

  12. Bhatt LK, Veeranjaneyulu A. Minocycline with aspirin: an approach to attenuate diabetic nephropathy in rats. Renal Fail. 2011;33:72–8.

    Article  CAS  Google Scholar 

  13. Tesch GH, Allen TJ. Rodent models of streptozotocin-induced diabetic nephropathy. Nephrology. 2007;12:261–6.

    Article  PubMed  Google Scholar 

  14. Jayanthi R, Subash P. Antioxidant effect of caffeic acid on oxytetracycline induced lipid peroxidation in albino rats. Indian J Clin Biochem. 2010;25:371–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Okutana H, Ozcelikb N, Yilmazb HR, Uzb E. Effects of caffeic acid phenethyl ester on lipid peroxidation and antioxidant enzymes in diabetic rat heart. Clin Biochem. 2005;38:191–6.

    Article  CAS  Google Scholar 

  16. Bancroft JD, Stevens A. Theory and practice of histological techniques. 4th ed. London: Churchill Livingstone; 1996.

    Google Scholar 

  17. Dweep H, Sticht C, Pandey P, Gretz N. miRWalk—database: prediction of possible miRNA binding sites by “walking” the genes of three genomes. J Biomed Inf. 2011;44:839–47.

    Article  CAS  Google Scholar 

  18. Paraskevopoulou MD, Georgakilas G, Kostoulas N, Vlachos IS, Vergoulis T, Reczko M, et al. DIANA-microT web server v5.0: Service integration into miRNA functional analysis workflows. Nucleic Acids Research. 2013; 41(Web Server issue), W169– W173 http://diana.cslab.ece.ntua.gr/pathways/.

  19. Jin HY, Liu WJ, Park JH, Baek HS, Park TS. Effect of dipeptidyl peptidase-IV (DPP-IV) inhibitor (Vildagliptin) on peripheral nerves in streptozotocin induced diabetic rats. Arch Med Res. 2009;40:536–44.

    Article  CAS  PubMed  Google Scholar 

  20. Kolset SO, Reinholt FP, Jenssen T. Diabetic nephropathy and extracellular matrix. J Histochem Cytochem. 2012;60:976–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Viswanathan V, Snehalatha C, Kumutha R, Jayaraman M, Ramachandran A. Serum albumin levels in different stages of type 2 diabetic nephropathy patients. Indian J Nephrol. 2004;14:89–92.

    Google Scholar 

  22. Khan S, Bhat ZR, Jena G. Role of autophagy and histone deacetylases in diabetic nephropathy: current status and future perspectives. Genes Dis. 2016;3:211–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Jung UJ, Lee MK, Park YB, Jeon SM, Choi MS. Antihyperglycemic and antioxidant properties of caffeic acid in db/db mice. J Pharmacol Exp Ther. 2006;318:476–83.

    Article  CAS  PubMed  Google Scholar 

  24. Zafar M, Naqvi SN. Effects of STZ-induced diabetes on the relative weights of kidney, liver and pancreas in albino rats: a comparative study. Int J Morphol. 2010;28:135–42.

    Article  Google Scholar 

  25. Wang GG, Lu XH, Li W, Zhao X, Zhang C. Protective effects of luteolin on diabetic nephropathy in STZ-induced diabetic rats. Evid Based Complement Alternat Med. 2011;2011:323171.

    PubMed  PubMed Central  Google Scholar 

  26. Patel AN, Bandwane DD, Mhetre NK. Pomegranate (Punica granatum Linn.) leaves attenuate disturbed glucose homeostasis and hyperglycemia mediated hyperlipidemia and oxidative stress in streptozotocin induced diabetic rats. Eur J Integr Med. 2014;6:307–21.

    Article  Google Scholar 

  27. Chuang ST, Kuo YH, Su MJ. Antifibrotic effects of KS370G, a caffeamide derivative, in renal ischemia-reperfusion injured mice and renal tubular epithelial cells. Sci Rep. 2014;4:5814.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Weidberg H, Shpilka T, Shvets E, Abada A, Shimron F, Elazar Z. LC3 and GATE-16 N termini mediate membrane fusion processes required for autophagosome biogenesis. Dev Cell. 2011;20:444–54.

    Article  CAS  PubMed  Google Scholar 

  29. Vijayakurup V, Spatafora C, Tringali C, Jayakrishnan PC, Srinivas P, Gopala S. Phenethyl caffeate benzoxanthene lignan is a derivative of caffeic acid phenethyl ester that induces bystander autophagy in WiDr cells. Mol Biol Rep. 2014;41:85–94.

    Article  CAS  PubMed  Google Scholar 

  30. Motawia TK, Abdelazima SA, Darwisha HA, Elbaza EM, Shoumanb SA. Could caffeic acid phenethyl ester expand the antitumor effect of tamoxifen in breast carcinoma? Nutr Cancer. 2016;68:435–45.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank Dr. Adel Bakir (Professor of Pathology, Faculty of Veterinary Medicine, Cairo University, Egypt) for his kind cooperation in the histopathological examinations involved in this research.

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Affiliations

  1. Biochemistry Department, Faculty of Science, Ain Shams University, Abbassia, Cairo, Egypt

    Ahmed M. Salem, Aya S. Ragheb & Marwa G. A. Hegazy

  2. Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, P.O. box 1138, Abbassia, Cairo, Egypt

    Marwa Matboli & Sanaa Eissa

Authors
  1. Ahmed M. Salem
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  2. Aya S. Ragheb
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  3. Marwa G. A. Hegazy
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  4. Marwa Matboli
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  5. Sanaa Eissa
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Correspondence to Marwa G. A. Hegazy or Sanaa Eissa.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed and all procedures performed in studies involving animals were in accordance with the ethical standards of Institutional Ethical Committee.

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Salem, A.M., Ragheb, A.S., Hegazy, M.G.A. et al. Caffeic Acid Modulates miR-636 Expression in Diabetic Nephropathy Rats. Ind J Clin Biochem 34, 296–303 (2019). https://doi.org/10.1007/s12291-018-0743-0

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  • DOI: https://doi.org/10.1007/s12291-018-0743-0

Keywords

  • Diabetic nephropathy
  • Caffeic acid
  • miRNA