Human ileal bile acid transporter gene ASBT (SLC10A2) is transactivated by the glucocorticoid receptor

Jung, Diana

doi:10.1136/gut.53.1.78

Cited by 166 publications

(110 citation statements)

References 42 publications

(39 reference statements)

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“…2A). This is in line with previous reports (Jung et al, 2004;Kwon and Carey, 2004;Wojtal et al, 2009); however, our data indicate that reductions in mRNA levels of ASBT mRNA persist during remission, consonant with increased fecal excretion of BA in patients with CD in clinical remission (Rutgeerts et al, 1979) and suggesting that alternative BA absorption mechanisms cannot compensate for reduced ASBT function (Dawson et al, 2003). The underlying mechanism for reduced ASBT levels in CD is not fully understood.…”

Section: Discussionsupporting

confidence: 89%

Inflammatory Bowel Disease Alters Intestinal Bile Acid Transporter Expression

et al. 2014

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The enterohepatic circulation of bile acids (BAs) critically depends on absorption of BA in the terminal ileum and colon, which can be affected by inflammatory bowel disease (IBD). Diarrhea in IBD is believed to result in part from BA malabsorption (BAM). We explored whether IBD alters mRNA expression of key intestinal BA transporters, BA detoxifying systems, and nuclear receptors that regulate BA transport and detoxification. Using real-time polymerase chain reaction, mucosal biopsy specimens from the terminal ileum in Crohn's disease (CD) patients and from the descending colon in ulcerative colitis (UC) patients were assessed for mRNA expression. Levels were compared with healthy controls. The main ileal BA uptake transporter, the apical sodium dependent bile acid transporter, was downregulated in active CD and UC and in CD in remission. Other significant changes such as repression of breast cancer-related protein and sulphotransferase 2A1 were seen only during active disease. In UC, pancolitis (but not exclusively left-sided colitis) was associated with altered expression of major BA transporters [multidrug resistance-associated protein 3 (MRP3), MRP4, multidrug resistance gene 1, organic solute transporter a/b] and nuclear receptors (pregnane X receptor, vitamin D receptor) in the descending colon. UC pancolitis leads to broad changes and CD ileitis to selective changes in intestinal BA transporter expression. Early medical manipulation of intestinal BA transporters may help prevent BAM.

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Section: Discussionsupporting

confidence: 89%

Inflammatory Bowel Disease Alters Intestinal Bile Acid Transporter Expression

et al. 2014

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“…The polyclonal rabbit anti-human ASBT antibody was raised against the carboxyl-terminal 39 amino acids of human ASBT that was expressed as a glutathione S-transferase-ASBT fusion protein. This antibody has been used previously to measure ASBT protein expression in human ileal biopsies (13). The anti-FLAG M2 monoclonal (catalog number F3165), anti-Myc (catalog number M5546), and anti-␤-actin (catalog number A5441) antibodies were obtained from Sigma.…”

Section: Materials-[mentioning

confidence: 99%

The Heteromeric Organic Solute Transporter α-β, Ostα-Ostβ, Is an Ileal Basolateral Bile Acid Transporter

Dawson

Hubbert

Haywood

et al. 2005

Journal of Biological Chemistry

345

364

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Bile acids are transported across the ileal enterocyte brush border membrane by the well characterized apical sodium-dependent bile acid transporter (Asbt) Slc10a2; however, the carrier(s) responsible for transporting bile acids across the ileocyte basolateral membrane into the portal circulation have not been fully identified. Transcriptional profiling of wild type and Slc10a2 null mice was employed to identify a new candidate basolateral bile acid carrier, the heteromeric organic solute transporter (Ost)␣-Ost␤. By Northern blot analysis, Ost␣ and Ost␤ mRNA was detected only in mouse kidney and intestine, mirroring the horizontal gradient of expression of Asbt in the gastrointestinal tract. Analysis of Ost␣ and Ost␤ protein expression by immunohistochemistry localized both subunits to the basolateral surface of the mouse ileal enterocyte. The transport properties of Ost␣-Ost␤ were analyzed in stably transfected Madin-Darby canine kidney cells. Coexpression of mouse Ost␣-Ost␤, but not the individual subunits, stimulated Na ؉ -independent bile acid uptake and the apical-to-basolateral transport of taurocholate. In contrast, basolateral-to-apical transport was not affected by Ost␣-Ost␤ expression. Co-expression of Ost␣ and Ost␤ was required to convert the Ost␣ subunit to a mature glycosylated endoglycosidase H-resistant form, suggesting that co-expression facilitates the trafficking of Ost␣ through the Golgi apparatus. Immunolocalization studies showed that co-expression was necessary for plasma membrane expression of both Ost␣ and Ost␤. These results demonstrate that the mouse Ost␣-Ost␤ heteromeric transporter is a basolateral bile acid carrier and may be responsible for bile acid efflux in ileum and other ASBT-expressing tissues.

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“…These changes are expected to increase BA uptake and possibly reduce cholesterol absorption, a putative mechanism of action of the hypolipemic drugs fibrates [43] . Corticoids are also known to upregulate ASBT expression [46] . Because BA ileal uptake is inhibited in intestinal inflammation and probably contributes to diarrhea, corticoid treatment may be specifically useful in this setting.…”

Section: Regulation Of Intestinal Ba Transportmentioning

confidence: 99%

Intestinal bile acid physiology and pathophysiology

Martínez‐Augustin¹,

Medina²

2008

WJG

135

114

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Bile acids (BAs) have a long established role in fat digestion in the intestine by acting as tensioactives, due to their amphipathic characteristics. BAs are reabsorbed very efficiently by the intestinal epithelium and recycled back to the liver via transport mechanisms that have been largely elucidated. The transport and synthesis of BAs are tightly regulated in part by specific plasma membrane receptors and nuclear receptors. In addition to their primary effect, BAs have been claimed to play a role in gastrointestinal cancer, intestinal inflammation and intestinal ionic transport. BAs are not equivalent in any of these biological activities, and structural requirements have been generally identified. In particular, some BAs may be useful for cancer chemoprevention and perhaps in inflammatory bowel disease, although further research is necessary in this field. This review covers the most recent developments in these aspects of BA intestinal biology.

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Human ileal bile acid transporter gene ASBT (SLC10A2) is transactivated by the glucocorticoid receptor

Cited by 166 publications

References 42 publications

Inflammatory Bowel Disease Alters Intestinal Bile Acid Transporter Expression

Inflammatory Bowel Disease Alters Intestinal Bile Acid Transporter Expression

The Heteromeric Organic Solute Transporter α-β, Ostα-Ostβ, Is an Ileal Basolateral Bile Acid Transporter

Intestinal bile acid physiology and pathophysiology

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