Curcumin suppresses epithelial-mesenchymal transition of renal tubular epithelial cells through the inhibition of Akt/mTOR pathway

Biological and Pharmaceutical Bulletin

Volumn 40, Issue 1, 2017, Pages 17-24

  Zhu, Fang Qiang ^a   Chen, Min Jia ^a   Zhu, Ming ^a   Zhao, Rong Seng ^a   Qiu, Wei ^a   Xu, Xiang ^a   Liu, Hong ^b   Zhao, Hong Wen ^b   Yu, Rong Jie ^b   Wu, Xiong Fei ^b   Zhang, Keqin ^b   Huang, Hong ^a  

^a THIRD MILITARY MEDICAL UNIVERSITY   (China)

^b THIRD MILITARY MEDICAL UNIVERSITY   (China)

Author keywords

Curcumin; Epithelial to mesenchymal transition; Mammalian target of rapamycin (mTOR) pathway; Renal fibrosis; Renal tubular epithelial cell; Transforming growth factor 1 (TGF 1)

Indexed keywords

ALPHA SMOOTH MUSCLE ACTIN; CALVASCULIN; CURCUMIN; CYTOKERATIN; MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; S6 KINASE; TRANSFORMING GROWTH FACTOR BETA1; UVOMORULIN; VIMENTIN; ACTA2 PROTEIN, HUMAN; ACTIN; CADHERIN; CALCIUM BINDING PROTEIN; CDH1 PROTEIN, HUMAN; FSP1 PROTEIN, HUMAN; KERATIN; MTOR PROTEIN, HUMAN; TARGET OF RAPAMYCIN KINASE;

ARTICLE; CELL PROLIFERATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; EPITHELIAL MESENCHYMAL TRANSITION; HUMAN; HUMAN CELL; KIDNEY TUBULE CELL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; CELL LINE; CELL SURVIVAL; CYTOLOGY; DRUG EFFECTS; EPITHELIUM CELL; GENETICS; KIDNEY PROXIMAL TUBULE; METABOLISM;

ACTINS; CADHERINS; CALCIUM-BINDING PROTEINS; CELL LINE; CELL SURVIVAL; CURCUMIN; EPITHELIAL CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; HUMANS; KERATINS; KIDNEY TUBULES, PROXIMAL; PROTO-ONCOGENE PROTEINS C-AKT; TOR SERINE-THREONINE KINASES; TRANSFORMING GROWTH FACTOR BETA1; VIMENTIN;

EID: 85007565940     PISSN: 09186158     EISSN: 13475215     Source Type: Journal    
DOI: 10.1248/bpb.b16-00364     Document Type: Article

References (41)

1. Iwano M, Plieth D, Danoff TM, Xue C, Okada H, Neilson EG. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J. Clin. Invest., 110, 341-350 (2002).
2. Kalluri R, Neilson EG. Epithelial-mesenchymal transition and its implications for fibrosis. J. Clin. Invest., 112, 1776-1784 (2003).
3. Zeisberg M, Duffield JS. Resolved: EMT produces fibroblasts in the kidney. J. Am. Soc. Nephrol., 21, 1247-1253 (2010).
4. Derynck R, Zhang YE. Smad-dependentand Smad-independent pathways in TGF-beta family signalling. Nature, 425, 577-584 (2003).
5. Liu Y. Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance, molecular mechanism, and therapeutic intervention. J. Am. Soc. Nephrol., 15, 1-12 (2004).
6. Aggarwal BB, Sung B. Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends Pharmacol. Sci., 30, 85-94 (2009).
7. Kuwabara N, Tamada S, Iwai T, Teramoto K, Kaneda N, Yukimura T, Nakatani T, Miura K. Attenuation of renal fibrosis by curcumin in rat obstructive nephropathy. Urology, 67, 440-446 (2006).
8. Bruck R, Ashkenazi M, Weiss S, Goldiner I, Shapiro H, Aeed H, Genina O, Helpern Z, Pines M. Prevention of liver cirrhosis in rats by curcumin. Liver Int., 27, 373-383 (2007).
9. Bridle KR, Popa C, Morgan ML, Sobbe AL, Clouston AD, Fletcher LM, Crawford DH. Rapamycin inhibits hepatic fibrosis in rats by attenuating multiple profibrogenic pathways. Liver Transpl., 15, 1315-1324 (2009).
10. Punithavathi D, Venkatesan N, Babu M. Curcumin inhibition of bleomycin-induced pulmonary fibrosis in rats. Br. J. Pharmacol., 131, 169-172 (2000).
11. Loeffler I, Wolf G. Transforming growth factor-? and the progression of renal disease. Nephrol. Dial. Transplant., 29 (Suppl 1), i37-i45 (2014).
12. Farahpour MR, Dilmaghanian A, Faridy M, Karashi E. Topical Moltkia coerulea hydroethanolic extract accelerates the repair of excision wound in a rat model. Chin. J. Traumatol., 19, 97-103 (2016).
13. Grille SJ, Bellacosa A, Upson J, Klein-Szanto AJ, van Roy F, Lee-Kwon W, Donowitz M, Tsichlis PN, Larue L. The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res., 63, 2172-2178 (2003).
14. Tao Y, Kim J, Schrier RW, Edelstein CL. Rapamycin markedly slows disease progression in a rat model of polycystic kidney disease. J. Am. Soc. Nephrol., 16, 46-51 (2005).
15. Barnes EA, Kenerson HL, Jiang X, Yeung RS. Tuberin regulates E-cadherin localization: implications in epithelial-mesenchymal transition. Am. J. Pathol., 177, 1765-1778 (2010).
16. Bieri M, Oroszlan M, Zuppinger C, Mohacsi PJ. Biosynthesis and expression of VE-cadherin is regulated by the PI3K/mTOR signaling pathway. Mol. Immunol., 46, 866-872 (2009).
17. Lieberthal W, Levine JS. The role of the mammalian target of rapamycin (mTOR) in renal disease. J. Am. Soc. Nephrol., 20, 2493-2502 (2009).
18. Lloberas N, Cruzado JM, Franquesa M, Herrero-Fresneda I, Torras J, Alperovich G, Rama I, Vidal A, Grinyó JM. Mammalian target of rapamycin pathway blockade slows progression of diabetic kidney disease in rats. J. Am. Soc. Nephrol., 17, 1395-1404 (2006).
19. Syed F, Sherris D, Paus R, Varmeh S, Singh S, Pandolfi PP, Bayat A. Keloid disease can be inhibited by antagonizing excessive mTOR signaling with a novel dual TORC1/2 inhibitor. Am. J. Pathol., 181, 1642-1658 (2012).
20. Jung KY, Dean D, Jiang J, Gaylor S, Griffith WH, Burghardt RC, Parrish AR. Loss of N-cadherin and alpha-catenin in the proximal tubules of aging male Fischer 344 rats. Mech. Ageing Dev., 125, 445-453 (2004).
21. Kreidberg JA, Symons JM. Integrins in kidney development, function, and disease. Am. J. Physiol. Renal Physiol., 279, F233-F242 (2000).
22. Gaedeke J, Noble NA, Border WA. Curcumin blocks multiple sites of the TGF-? signaling cascade in renal cells. Kidney Int., 66, 112-120 (2004).
23. Lieberthal W, Levine JS. The role of the mammalian target of rapamycin (mTOR) in renal disease. J. Am. Soc. Nephrol., 20, 2493-2502 (2009).
24. Lamouille S, Derynck R. Cell size and invasion in TGF-betainduced epithelial to mesenchymal transition is regulated by activation of the mTOR pathway. J. Cell Biol., 178, 437-451 (2007).
25. Inazaki K, Kanamaru Y, Kojima Y, Sueyoshi N, Okumura K, Kaneko K, Yamashiro Y, Ogawa H, Nakao A. Smad3 deficiency attenuates renal fibrosis, inflammation,and apoptosis after unilateral ureteralobstruction. Kidney Int., 66, 597-604 (2004).
26. Zeisberg M, Hanai J, Sugimoto H, Mammoto T, Charytan D, Strutz F, Kalluri R. BMP-7 counteracts TGF-beta1-induced epithelialto-mesenchymal transition and reverses chronic renal injury. Nat. Med., 9, 964-968 (2003).
27. Tan RJ, Zhou D, Zhou L, Liu Y. Wnt/?-catenin signaling and kidney fibrosis. Kidney Int. Suppl., 4, 84-90 (2014).
28. Maheshwari RK, Singh AK, Gaddipati J, Srimal RC. Multiple biological activities of curcumin: a short review. Life Sci., 78, 2081-2087 (2006).
29. Sa G, Das T. Anti cancer effects of curcumin: cycle of life and death. Cell Div., 3, 14-20 (2008).
30. Syng-Ai C, Kumari AL, Khar A. Effect of curcumin on normal and tumor cells: Role of glutathione and bcl-2. Mol. Cancer Ther., 3, 1101-1108 (2004).
31. Khar A, Ali AM, Pardhasaradhi BVV, Varalakshmi Ch, Anjum R, Kumari AL. Induction of stress response renders human tumor cell lines resistant to curcumin-mediated apoptosis: role of reactive oxygen intermediates. Cell Stress Chaperones, 6, 368-376 (2001).
32. Kim SJ, Son TG, Park HR, Park M, Kim MS, Kim HS, Chung HY, Mattson MP, Lee J. Curcumin stimulates proliferation of embryonic neural progenitor cells and neurogenesis in the adult hippocampus. J. Biol. Chem., 283, 14497-14505 (2008).
33. Bhattacharyya S, Mandal D, Saha B, Sen GS, Das T, Sa G. Curcumin prevents tumor-induced T cell apoptosis through Stat-5amediated Bcl-2 induction. J. Biol. Chem., 282, 15954-15964 (2007).
34. Ten Dijke P, Goumans M-J, Itoh F, Itoh S. Regulation of cell proliferation by Smad proteins. J. Cell. Physiol., 191, 1-16 (2002).
35. Siegel PM, Massagué J. Cytostatic and apoptotic actions of TGF-?1 in homeostasis and cancer. Nat. Rev. Cancer, 3, 807-820 (2003).
36. Johnson SA, Spurney RF. Twenty years after ACEIs and ARBs: emerging treatment strategies for diabetic nephropathy. Am. J. Physiol. Renal Physiol., 309, F807-F820 (2015).
37. Attisano L, Wrana JL. Signal transduction by the TGF-beta superfamily. Science, 296, 1646-1647 (2002).
38. Doi S, Zou Y, Togao O, Pastor JV, John GB, Wang L, Shiizaki K, Gotschall R, Schiavi S, Yorioka N, Takahashi M, Boothman DA, Kuro-o M. Klotho inhibits transforming growth factor-beta1 (TGFbeta1) signaling and suppresses renalfibrosis and cancer metastasis in mice. J. Biol. Chem., 286, 8655-8665 (2011).
39. Jain S, Bicknell GR, Whiting PH, Nicholson ML. Rapamycin reduces expression of fibrosis-associated genes in an experimental model of renalischaemia reperfusion injury. Transplant. Proc., 33, 556-558 (2001).
40. Copeland JW, Beaumont BW, Merrilees MJ, Pilmore HL. Epithelial-to-mesenchymal transition of human proximal tubular epithelial cells: effects of rapamycin, mycophenolate, cyclosporin, azathioprine, and methylprednisolone. Transplantation, 83, 809-814 (2007).
41. Sharma RA, Euden SA, Platton SL, Cooke DN, Shafayat A, Hewitt HR, Marczylo TH, Morgan B, Hemingway D, Plummer SM, Pirmohamed M, Gescher AJ, Steward WP. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin. Cancer Res., 10, 6847-6854 (2004).