Adaptive regulation of the ileal apical sodium dependent bile acid transporter (ASBT) in patients with obstructive cholestasis

Hruz, P.; Zimmermann, C.; Gutmann, H.; Degen, L.; Beuers, U.; Terracciano, L.; Drewe, J.; Beglinger, C.
March 2006
Gut;Mar2006, Vol. 55 Issue 3, p395
Academic Journal
Background/aims: The apical sodium dependent bile acid transporter ASBT (SLC10A2) contributes substantially to the enterohepatic circulation of bile acids by their reabsorption from the intestine. In the rat, its adaptive regulation was observed in the kidneys, cholangiocytes, and terminal ileum after bile duct ligation. Whether adaptive regulation of the human intestinal ASBT exists during obstructive cholestasis is not known. Methods: Human ASBT mRNA expression along the intestinal tract was analysed by real time polymerase chain reaction in biopsies of 14 control subjects undergoing both gastroscopy and colonoscopy. Their duodenal ASBT mRNA expression was compared with 20 patients with obstructive cholestasis. Additionally, in four patients with obstructive cholestasis, duodenal ASBT mRNA expression was measured after reconstitution of bile flow. Results: Normalised ASBT expression in control subjects was highest (mean arbitrary units (SEM)) in the terminal ileum (1010 (330)). Low ASBT expression was found in colonic segments (8.3 (5), 4.9 (0.9), 4.8 (1.7), and 1.1 (0.2) in the ascending, transverse, descending, and sigmoid colon, respectively). Duodenal ASBT expression in control subjects (171.8 (20.3)) was found to be approximately fourfold higher compared with patients with obstructive cholestasis (37.9 (6.5); p<0.0001). Individual ASBT mRNA expression was inversely correlated with bile acid and bilirubin plasma concentrations. In four cholestatic patients, average ASBT mRNA increased from 76 (18) before to 113 (18) after relief of cholestasis (NS). Immunohistochemical assessment indicated that ASBT protein was expressed on the apical surface of duodenal epithelial cells. Conclusion: Obstructive cholestasis in humans leads to downregulation of ASBT mRNA expression in the distal part of the human duodenum.


Related Articles

  • CROHN'S DISEASE AND THE NOD2 GENE: A ROLE FOR PANETH CELLS. Lala, S.G.; Ogura, Y.; Hor, S.K.; Abeya, M.; Osborne, C.; Davies, S.; Ogunbiyi, O.; Nunez, G.; Keshav, S. // Gut;Apr2003 Supplement 1, Vol. 52, pA39 

    Background and Aims: Mutations in the NOD2 gene predisposing to Crohn's disease (CD) are predominantly associated with terminal ileal disease. The mechanisms by which these mutations cause ileitis are unknown, as NOD2 is most highly expressed by circulating peripheral blood monocytes, which are...

  • Glutathione Depletion Exacerbates Methylenedianiline Toxicity to Biliary Epithelial Cells and Hepatocytes in Rats. Kanz, M. F.; Dugas, T. R.; Liu, H.; Santa Cruz, V. // Toxicological Sciences;Aug2003, Vol. 74 Issue 2, p447 

    Methylenedianiline (DAPM) initially injures epithelial cells of major bile ducts, which is followed by cholestasis, cholangitis, and hepatocellular damage. This pattern of biliary injury resembles that produced by α-naphthylisothiocyanate (ANIT), a classic bile duct toxicant. Our goal was to...

  • How to induce non-polarized cells of hepatic origin to express typical hepatocyte polarity: generation of new highly polarized cell models with developed and functional bile canaliculi. Peng, Xu; Grosse, Brigitte; Tiec, Benoît; Nicolas, Valérie; Delagebeaudeuf, Claire; Bedda, Tarik; Decaens, Catherine; Cassio, Doris // Cell & Tissue Research;Jan2006, Vol. 323 Issue 2, p233 

    Few in vitro models expressing complex hepatocyte polarity are available. We used the unpolarized rat Fao cell line to isolate the polarized WIF-B line. These complex rat-human hybrid cells form functional simple bile canaliculi. To obtain Fao-derived polarized models with a simpler chromosome...

  • Autophagy Controls an Intrinsic Host Defense to Bacteria by Promoting Epithelial Cell Survival: A Murine Model. Chang, Sun-Young; Lee, Se-Na; Yang, Jin-Young; Kim, Dong Wook; Yoon, Joo-Heon; Ko, Hyun-Jeong; Ogawa, Michinaga; Sasakawa, Chihiro; Kweon, Mi-Na // PLoS ONE;Nov2013, Vol. 8 Issue 11, p1 

    Cell death is a critical host response to regulate the fate of bacterial infections, innate immune responses, and ultimately, disease outcome. Shigellaspp. invade and colonize gut epithelium in human and nonhuman primates but adult mice are naturally resistant to intra-gastric Shigella...

  • A novel diamino-pyridine derivative (IS-741) attenuates rat ileitis induced by trinitrobenzene sulfonic acid. Fukunaga, Tetsuya; Tsujikawa, Tomoyuki; Sasaki, Masaya; Fujiyama, Yoshihide; Bamba, Tadao; Fujimiya, Mineko // Journal of Gastroenterology;2003, Vol. 38 Issue 5, p451 

    Background: The etiology and pathogenesis of inflammatory bowel disease remain unknown. However, neutrophil infiltration into the inflammatory lesion is an important process in inflammatory bowel disease. In this study, we used rat trinitrobenzene sulfonic acid (TNBS) ileitis as a...

  • Intestinal Epithelial Cells with Impaired Autophagy Lose Their Adhesive Capacity in the Presence of TNF-α. Saito, Masaya; Katsuno, Tatsuro; Nakagawa, Tomoo; Sato, Toru; Noguchi, Yoshiko; Sazuka, Sayuri; Saito, Keiko; Arai, Makoto; Yokote, Koutaro; Yokosuka, Osamu // Digestive Diseases & Sciences;Aug2012, Vol. 57 Issue 8, p2022 

    Background and Objectives: Genome-wide association studies have revealed a link between autophagy-related (ATG) genes and susceptibility to Crohn's disease. This suggests underlying involvement of autophagy impairment in the pathogenesis of Crohn's disease. This study was performed to...

  • Butyricicoccus pullicaecorum in inflammatory bowel disease. Eeckhaut, Venessa; Machiels, Kathleen; Perrier, Clémentine; Romero, Carlos; Maes, Sofie; Flahou, Bram; Steppe, Marjan; Haesebrouck, Freddy; Sas, Benedikt; Ducatelle, Richard; Vermeire, Severine; Van Immerseel, Filip // Gut;Dec2013, Vol. 62 Issue 12, p1745 

    Objective: Many species within the phylum Firmicutes are thought to exert anti-inflammatory effects. We quantified bacteria belonging to the genus Butyricicoccus in stools of patients with ulcerative colitis (UC) and Crohn's disease (CD). We evaluated the effect of Butyricicoccus pullicaecorum...

  • Slipping the barrier: how variants in CARD 15 could alter permeability of the intestinal wall and population health. Schreiber, S. // Gut;Mar2006, Vol. 55 Issue 3, p308 

    The increased intestinal permeability in Crohn's disease is associated with the presence of variants in the CARD15 gene that are regarded as causative for Crohn's disease, suggesting a genetic rather than an environmental background for intestinal Barrier dysfunction in Crohn's disease.

  • Acute ileitis. Morain, C.Q. // British Medical Journal (Clinical Research Edition);10/24/1981, Vol. 283 Issue 6299, p1075 

    Focuses on the distinction of acute ileitis from Crohn's disease. Cause of acute terminal ileitis; Relation of fistula formation in Crohn's disease to the severity of the disease in the ileum; Procedures to the diagnosis of Crohn's disease.


Read the Article


Sign out of this library

Other Topics