Research in the Shneider Laboratory is primarily focused on analyzing the molecular regulation of intestinal bile acid transport. Intestinal reclamation of bile acids is predominantly mediated by the apical sodium-dependent bile acid transporter (ASBT). Complex paradigms for the control of the…
more expression of ASBT under study, include particular patterns for tissue-specificity, ontogeny, and responses to intestinal resection, inflammation and alterations in bile acid homeostasis. Regulation of ASBT occurs both at a transcriptional and post-transcriptional level. Loss of function of ASBT in pathologic states is associated with bile acid induced diarrhea, while controlled loss of function has the potential to be used to treat hypercholesterolemia. In contrast, gain of function of ASBT may play a role in the overall pathogenesis of cholestasis. Research from the Shneider Laboratory has shown that hepatocyte nuclear factor 1-alpha and c-jun play an integral part in the basal transcriptional activation of ASBT. Inflammatory mediated down-regulation of ASBT is mediated by c-fos. Bile acid responsiveness of ASBT is species-specific. Simultaneous absence of cis-elements and trans-acting factors yields a lack of response in rats. Negative feedback in occurs via farnesoid x-receptor dependent pathways acting through the liver receptor homologue-1 and the retinoic acid receptor, respectively for mice and humans.
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