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MEMBRANE BILE ACID RECEPTOR TGR5 - A NEW TARGET IN THE STUDY OF METABOLIC, INFLAMMATORY AND NEOPLASTIC DISEASES

https://doi.org/10.20996/1819-6446-2016-12-3-344-350

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Abstract

TGR5 are G-protein-linked, membrane bile acids receptors that widely express in tissues of animals and humans. Namely tissue localization of TGR5 determines biological effects of activation of these receptors. This review focuses on the role of TGR5 as a new pharmacological target for the treatment of patients with metabolic syndrome, diabetes, obesity, atherosclerosis, liver disease and cancer processes.

About the Authors

O. M. Drapkina
State Research Centre for Preventive Medicine. Petroverigsky per. 10, Moscow, 101990 Russia
Russian Federation


E. I. Fomicheva
State Research Centre for Preventive Medicine. Petroverigsky per. 10, Moscow, 101990 Russia
Russian Federation


References

1. Maruyama T., Miyamoto Y., Nakamura T., et al. Identification of membrane-type receptor for bile acids (M-BAR). Biochemical and Biophysical Research Communications 2002; 298: 714-9.

2. Kawamata Y., Fujii R., Hosoya M., et al. A G protein-coupled receptor responsive to bile acids. Journal of Biological Chemistry 2003; 278: 9435-40.

3. Vassileva G., Golovko A., Markowitz L., et al. Targeted deletion of Gpbar1 protects mice from cholesterol gallstone formation. Biochemical Journal 2006; 398: 423-30.

4. Müssig K., Staiger H., Machicao F., et al. Preliminary report: genetic variation within the GPBAR1 geneis not associated with metabolic traits in white subjects at an increased risk for type 2 diabetes mellitus. Metabolism - Clinical and Experimental 2009;58:1809-11.

5. Hov J. R., Keitel V., Laerdahl J. K., et al. Mutational characterization of the bile acid receptor TGR5 in primary sclerosing cholangitis. PLoS ONE 2010; 5: e12403

6. Maruyama T., Tanaka K., Suzuki J. et al. Targeted disruption of G protein-coupled bile acid receptor 1 (Gpbar1/M-Bar) in mice. Journal of Endocrinology 2006; 191: 197-205.

7. Keitel V., Görg B., Bidmon H.J., et al. The bile acid receptor TGR5 (Gpbar-1) acts as a neurosteroid receptor in brain. Glia 2010; 58: 1794-805.

8. Alemi F., Kwon E., Poole D.P., et al. The TGR5 receptor mediates bile acid-induced itch and analgesia. Journal of Clinical Investigation 2013; 123: 1513-30.

9. Poole D.P., Godfrey C., Cattaruzza F., et al. Expression and function of the bile acid receptor GpBAR1 (TGR5) in the murine enteric nervous system. Neurogastroenterology and Motility 2010; 22: 814-25.

10. Fiorucci S, Mencarelli A, Palladino G, Cipriani S. Bile-acid-activated receptors: targeting TGR5 and far-nesoid-X-receptor in lipid and glucose disorders. Trends Pharmacol Sci 2009;30:570-80.

11. Cipriani S., Mencarelli A., Chini M.G., et al. The bile acid receptor GPBAR-1 (TGR5) modulates integrity of intestinal barrier and immune response to experimental colitis. PLoS ONE 2011; 6: e25637

12. Vassileva G., Hu W., Hoos L., et al. Gender-dependent effect of Gpbar1 genetic deletion on the metabolic profiles of diet-induced obese mice. Journal of Endocrinology 2010; 205: 225-32.

13. Calmus Y., Guechot J., Podevin P., et al. Differential effects of chenodeoxycholic and ursodeoxycholic acids on interleukin 1, interleukin 6 and tumor necrosis factor-alpha production by monocytes. He-patology 1992; 16: 719-23.

14. Keitel V., Donner M., Winandy S., et al. Expression and function of the bile acid receptor TGR5 in Kupf-fer cells. Biochemical and Biophysical Research Communications 2008; 372: 78-84.

15. Pols T. W. H., Nomura M., Harach T., et al. TGR5 activation inhibits atherosclerosis by reducing macrophage inflammation and lipid loading. Cell Metabolism 2011; 14: 747-57.

16. Ichikawa R., Takayama T., Yoneno K., et al. Bile acids induce monocyte differentiation toward interleukin-12 hypo-producing dendritic cells via a TGR5-dependent pathway. Immunology 2012; 136: 153-62.

17. Kida T., Tsubosaka Y., Hori M., et al. Bile acid receptor TGR5 agonism induces NO production and reduces monocyte adhesion in vascular endothelial cells Arteriosclerosis, Thrombosis, and Vascular Biology 2013; 33: 1663-9.

18. Duboc H., Aelion H., Rainteau D., et al. Crosstalk between the hepatologist and the cardiologist: a future place for the lithocholic acid as a coronary atheroma risk factor? Hepatology 2012; 56: 24-6.

19. Watanabe M., Houten S.M., Mataki C., et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 2006; 439: 484-9.

20. Thomas C., Gioiello A., Noriega L., et al. TGR5-mediated bile acid sensing controls glucose home-ostasis. Cell Metabolism 2009; 10:167-77.

21. Wu T., Bound M.J., Standfield S.D., et al. Effects of rectal administration of taurocholic acid on glucagon-like peptide-1 and peptide YY secretion in healthy humans. Diabetes, Obesity and Metabolism 2013; 15: 474-7.

22. Evans K. A., Budzik B.W., Ross S.A., et al. Discovery of 3-aryl-4-isoxazolecarboxamides as TGR5 receptor agonists. Journal of Medicinal Chemistry 2009; 52: 7962-5.

23. Sato H., Genet C., Strehle A., et al. Anti-hyperglycemic activity of a TGR5 agonist isolated from Olea europaea. Biochemical and Biophysical Research Communications 2007; 362: 793-8.

24. Pols T. W. H., Noriega L.G., Nomura M., et al. The bile acid membrane receptor TGR5: a valuable metabolic target. Digestive Diseases 2011; 29: 37-44.

25. Porez G., Prawitt J., Gross B., Staels B. Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease. Journal of Lipid Research 2012; 53: 1723-37.

26. Debruyne P. R., Bruyneel E.A., Li X., et al. The role of bile acids in carcinogenesis. Mutation Research 2001; 480-481: 359-69.

27. Bernstein C., Holubec H., Bhattacharyya A.K., et al. Carcinogenicity of deoxycholate, a secondary bile acid. Archives of Toxicology 2011; 85: 863-71.

28. Hong J., Behar J., Wands J., et al. Role of a novel bile acid receptor TGR5 in the development of oesophageal adenocarcinoma. Gut 2010; 59: 170-80.

29. Lundegårdh G., Adami H.O., Helmick C., et al. Stomach cancer after partial gastrectomy for benign ulcer disease. New England Journal of Medicine 1988; 319: 195-200.

30. Lundegårdh G., Adami H.O., Helmick C., Zack M. Risk of cancer following partial gastrectomy for be nign ulcer disease. British Journal of Surgery 1994; 81: 1164-7.

31. Yasuda H., Hirata S., Inoue K., et al. Involvement of membrane-type bile acid receptor M-BAR/TGR5 in bile acid-induced activation of epidermal growth factor receptor and mitogen-activated protein kinases in gastric carcinoma cells. Biochemical and Biophysical Research Communications 2007; 354: 154-9.

32. Cao W., Tian W., Hong J., et al. Expression of bile acid receptor TGR5 in gastric adenocarcinoma. American Journal of Physiology - Gastrointestinal and Liver Physiology 2013; 304: G322-G327.

33. Chen W.-D., Yu D., Forman B.M., et al. The deficiency of G-protein-coupled bile acid receptor gpbar1 (TGR5) enhances chemically-induced liver carcinogenesis. Hepatology 2013;57(2):656-66.

34. He G., Yu G.-Y., Temkin V., et al. Hepatocyte IKKbeta/NF-kappaB inhibits tumor promotion and progression by preventing oxidative stress-driven STAT3 activation. Cancer Cells 2010; 17: 286-97.

35. Marzioni M., Ueno Y., Glaser S., et al. Cytoprotective effects of taurocholic acid feeding on the biliary tree after adrenergic denervation of the liver. Liver International 2007; 27: 558-68.

36. Marzioni M., LeSage G.D., Glaser S., et al. Taurocholate prevents the loss of intrahepatic bile ducts due to vagotomy in bile duct-ligated rats. American Journal of Physiology - Gastrointestinal and Liver Physiology 2003; 284: G837-G852.

37. Keitel V., Reinehr R., Gatsios P., et al. The G-protein coupled bile salt receptor TGR5 is expressed in liver sinusoidal endothelial cells. Hepatology 2007; 45: 695-704.

38. Reinehr R., Häussinger D. Inhibition of bile salt-induced apoptosis by cyclic AMP involves serine/thre onine phosphorylation of CD95. Gastroenterology 2004; 126: 249-62.

39. Alemi F. Poole D.P., Chiu J., et al. The receptor TGR5 mediates the prokinetic actions of intestinal bile acids and is required for normal defecation in mice. Gastroenterology 2012; 144(1):145-54.

40. Camilleri M., Vazquez-Roque M.I., Carlson P., et al. Association of bile acid receptor TGR5 variation and transit in health and lower functional gastrointestinal disorders. Neurogastroenterology and Motility 2011; 23: 995-9.

41. Potthoff M. J., Potts A., He T., et al. Colesevelam suppresses hepatic glycogenolysis by TGR5-mediated induction of GLP-1 action in DIO mice. American Journal of Physiology - Gastrointestinal and Liver Physiology 2013; 304: G371-G380.

42. Gerova V. A., Stoynov S.G., Katsarov D.S., Svinarov D.A.. Increased intestinal permeability in inflammatory bowel diseases assessed by iohexol test. World Journal of Gastroenterology 2011; 17: 2211-5.

43. Bertiaux-Vandaële N., Youmba S.B., Belmonte L., et al. The expression and the cellular distribution of the tight junction proteins are altered in irritable bowel syndrome patients with differences according to the disease subtype. American Journal of Gastroenterology 2011; 106: 2165-73.

44. Lavoie B., Balemba O.B., Godfrey C., et al. Hydrophobic bile salts inhibit gallbladder smooth muscle function via stimulation of GPBAR1 receptors and activation of KATP channels. Journal of Physiology (London) 2010; 588 (Pt 17): 3295-305.

45. Keitel V., Ullmer C., Häussinger D. The membrane-bound bile acid receptor TGR5 (Gpbar-1) is localized in the primary cilium of cholangiocytes. Biological Chemistry 2010; 391: 785-9.

46. Keitel V., Häussinger D. TGR5 in the biliary tree. Digestive Diseases 2011; 29: 45-7.

47. Keitel V, Cupisti K, Ullmer C, et al. The membrane-bound bile acid receptor TGR5 is localized in the epithelium of human gallbladders. Hepatology 2009;50:861-70.

48. Hov J.R., Keitel V., Laerdahl J.K., et al. Mutational characterization of the bile acid receptor TGR5 in primary sclerosing cholangitis. PLoS ONE 2010; 5: e12403.


For citation:


Drapkina O.M., Fomicheva E.I. MEMBRANE BILE ACID RECEPTOR TGR5 - A NEW TARGET IN THE STUDY OF METABOLIC, INFLAMMATORY AND NEOPLASTIC DISEASES. Rational Pharmacotherapy in Cardiology. 2016;12(3):344-350. https://doi.org/10.20996/1819-6446-2016-12-3-344-350

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