Bile acid activated receptors are targets for regulation of integrity of gastrointestinal mucosa

详细信息    查看全文

• 作者：Eleonora Distrutti ; Luca Santucci ; Sabrina Cipriani…
• 刊名：Journal of Gastroenterology
• 出版年：2015
• 出版时间：July 2015
• 年：2015
• 卷：50
• 期：7
• 页码：707-719
• 全文大小：1,173 KB
• 参考文献：1.Fiorucci S, Zampella A, Distrutti E. Development of FXR, PXR and CAR agonists and antagonists for treatment of liver disorders. Curr Top Med Chem. 2012;12:605-4.PubMed View Article
  2.Fiorucci S, Cipriani S, Baldelli F, et al. Bile acid-activated receptors in the treatment of dyslipidemia and related disorders. Prog Lipid Res. 2010;49:171-5.PubMed View Article
  3.Fiorucci S, Mencarelli A, Palladino G, et al. Bile-acid-activated receptors: targeting TGR5 and farnesoid-X-receptor in lipid and glucose disorders. Trends Pharmacol Sci. 2009;30:570-0.PubMed View Article
  4.Fiorucci S, Rizzo G, Donini A, et al. Targeting farnesoid X receptor for liver and metabolic disorders. Trends Mol Med. 2007;13:298-09.PubMed View Article
  5.Swanson HI, Wada T, Xie W, et al. Role of nuclear receptors in lipid dysfunction and obesity-related diseases. Drug Metab Dispos. 2013;41:1-1.PubMed Central PubMed View Article
  6.Fiorucci S, Mencarelli A, Distrutti E, et al. Farnesoid X receptor: from medicinal chemistry to clinical applications. Future Med Chem. 2012;4:877-1.PubMed View Article
  7.Kong B, Wang L, Chiang JY, et al. Mechanism of tissue-specific farnesoid X receptor in suppressing the expression of genes in bile-acid synthesis in mice. Hepatology. 2012;56:1034-3.PubMed Central PubMed View Article
  8.Wang L, Lee YK, Bundman D, et al. Redundant pathways for negative feedback regulation of bile acid production. Dev Cell. 2002;2:721-1.PubMed View Article
  9.Eloranta JJ, Meier PJ, Kullak-Ublick GA. Coordinate transcriptional regulation of transport and metabolism. Methods Enzymol. 2005;400:511-0.PubMed View Article
  10.Kullak-Ublick GA, Stieger B, Meier PJ. Enterohepatic bile salt transporters in normal physiology and liver disease. Gastroenterology. 2004;126:322-2.PubMed View Article
  11.Owen BM, Mangelsdorf DJ, Kliewer SA. Tissue-specific actions of the metabolic hormones FGF15/19 and FGF21. Trends Endocrinol Metab. 2014. doi:10.-016/?j.?tem.-014.-0.-02 .PubMed
  12.Inagaki T, Choi M, Moschetta A, et al. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab. 2005;2:217-5.PubMed View Article
  13.Lieu T, Jayaweera G, Bunnett NW. GPBA: a GPCR for bile acids and an emerging therapeutic target for disorders of digestion and sensation. Br J Pharmacol. 2014;171:1156-6.PubMed Central PubMed View Article
  14.Poole DP, Godfrey C, Cattaruzza F, et al. Expression and function of the bile acid receptor GP-BAR1 (TGR5) in the murine enteric nervous system. Neurogastroenterol Motil. 2010;22:814-5.PubMed Central PubMed View Article
  15.Alemi F, Poole DP, Chiu J, et al. The receptor TGR5 mediates the prokinetic actions of intestinal bile acids and is required for normal defecation in mice. Gastroenterology. 2013;144:145-4.PubMed View Article
  16.Lieu T, Jayaweera G, Zhao P, et al. The bile acid receptor TGR5 activates the TRPA1 channel to induce itch in mice. Gastroenterology. 2014;147:1417-8.PubMed View Article
  17.Camilleri M, Vazquez-Roque MI, Carlson P, et al. Association of bile acid receptor TGR5 variation and transit in health and lower functional gastrointestinal disorders. Neurogastroenterol Motil. 2011;23:995-.PubMed Central PubMed View Article
  18.Katsuma S, Hirasawa A, Tsujimoto G. Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem Biophys Res Commun. 2005;329:386-0.PubMed View Article
  19.Cipriani S, Mencarelli A, Chini MG, et al. The bile acid receptor GPBAR-1 (TGR5) modulates integrity of intestinal barrier and immune response to experimental colitis. PLoS One. 2011. doi:10.-371/?journal.?pone.-025637 .
  20.Hov JR, Keitel V, Laerdahl JK, et al. Mutational characterization of the bile acid receptor TGR5 in primary sclerosing cholangitis. PLoS One. 2010. doi:10.-371/?journal.?pone.-012403 .PubMed Central PubMed
  21.Laine L. Review article: gastrointestinal bleeding with low-dose aspirin—what’s the risk? Aliment Pharmacol Ther. 2006;24:897-08.PubMed View Article
  22.Laine L, Smith R, Min K, et al. Systematic review: the lower gastrointestinal adverse effects of non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther. 2006;24:751-7.PubMed View Article
  23.Takeuchi K. Pathogenesis of NSAID-induced gastric damage: importance of cyclooxygenase inhibition and gastric hypermotility. World J Gastroenterol. 2012;18:2147-0.PubMed Central PubMed View Article
  24.Grosser T, Yu Y, Fitzgerald GA. Emotion recollected in tranquility: lessons learned from the COX-2 saga. Annu Rev Med. 2010;61:17-3.PubMed View Article
  25.Laine L, Jensen DM. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012;107:345-0.PubMed View Article
  26.Hawkey CJ, Karrasch JA, Szczepa?ski L, et al. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal anti-inflammatory drugs. N Engl J Med. 1998;338:727-4.
• 作者单位：Eleonora Distrutti (1)
  Luca Santucci (2)
  Sabrina Cipriani (3)
  Barbara Renga (4)
  Elisabetta Schiaroli (3)
  Patrizia Ricci (4)
  Annibale Donini (4)
  Stefano Fiorucci (4)
  
  1. Azienda Ospedaliera di Perugia, Perugia, Italy
  2. Azienda Unita-Sanitaria Locale Umbria 2, Perugia, Italy
  3. Dipartimento di Medicina, Università degli Studi di Perugia, Perugia, Italy
  4. Sezione di Gastroenterologia, Dipartimento di Scienze Chirurgiche e Biomediche, Nuova Facoltà di Medicina e Chirurgia, Università di Perugia, Edificio B-Piano III-Via Gambuli,1, S. Andrea delle Fratte-Perugia, 06132, Perugia, Italy
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Gastroenterology
  Oncology
  Surgical Oncology
  Hepatology
  Internal Medicine
  Colorectal Surgery
  
• 出版者：Springer Japan
• ISSN：1435-5922

文摘

Bile acids are the end product of cholesterol metabolism. Synthesized in the liver, primary bile acids are secreted by hepatocytes and are transformed by intestinal microbiota into secondary bile acids. In addition to their role in cholesterol and lipid absorption, bile acids act as signaling molecules activating a family of nuclear and G-protein-coupled receptors collectively known as bile acid activated receptors (BARs). These receptors are expressed at high density in enterohepatic tissues, but their expression occurs throughout the body and their activation mediates regulatory functions of bile acids on lipids and glucose metabolism and immunity. In the gastrointestinal tract, BARs maintain intestinal integrity, and their deletion makes the intestine more susceptible to the damage caused by acetylsalicylic acid and nonsteroidal anti-inflammatory drugs (NSAIDs). Deficiency in farnesoid X receptor and G-protein-coupled bile acid receptor?1 genes alters the expression/activity of cystathione γ-lyase and endothelial nitric oxide synthase, two genes involved in the synthesis of hydrogen sulfide and nitric oxide, i.e., two gaseous mediators that have been shown to be essential in maintaining the intestinal homeostasis. In addition, farnesoid X receptor regulates the expression of transporters required for secretion of phospholipid by hepatocytes. Because phospholids attenuate intestinal injury caused by acetylsalicylic acid and NSAIDs, BAR agonism could be exploited to protect the intestinal mucosa against injury caused by anti-inflammatory medications. This approach might be useful in the prevention of so-called NSAID enteropathy, a common clinical condition occurring in long-term users of NSAIDs, which is not effectively prevented either by cotreatment with proton pump inhibitors or by the use of coxibs.