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Article: Bile acids inhibit duodenal secretin expression via orphan nuclear receptor small heterodimer partner (SHP)

TitleBile acids inhibit duodenal secretin expression via orphan nuclear receptor small heterodimer partner (SHP)
Authors
KeywordsBile flow
Cholangiocyte
Choleresis
Liver
Issue Date2009
PublisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpgi.physiology.org/
Citation
American Journal Of Physiology - Gastrointestinal And Liver Physiology, 2009, v. 297 n. 1, p. G90-G97 How to Cite?
AbstractSmall heterodimer partner (SHP) is an orphan nuclear receptor in which gene expression can be upregulated by bile acids. It regulates its target genes by repressing the transcriptional activities of other nuclear receptors including NeuroD, which has been shown to regulate secretin gene expression. Here, we evaluated the regulation on duodenal secretin gene expression by SHP and selected bile acids, cholic acid (CA) and chenodeoxycholic acid (CDCA). In vitro treatment of CDCA or fexaramine elevated the SHP transcript level and occupancy on secretin promoter. The increase in the SHP level, induced by bile acid treatment or overexpression, reduced secretin gene expression, whereas this gene inhibitory effect was reversed by silencing of endogenous SHP. In in vivo studies, double-immunofluorescence staining demonstrated the coexpression of secretin and SHP in mouse duodenum. Feeding mice with 1% CA-enriched rodent chow resulted in upregulation of SHP and a concomitant decrease in secretin transcript and protein levels in duodenum compared with the control group fed with normal chow. A diet enriched with 5% cholestyramine led to a decrease in SHP level and a corresponding increase in secretin expression. Overall, this study showed that bile acids via SHP inhibit duodenal secretin gene expression. Because secretin is a key hormone that stimulates bile flow in cholangiocytes, this pathway thus provides a novel means to modulate secretin-stimulated choleresis in response to intraduodenal bile acids. Copyright © 2009 the American Physiological Society.
Persistent Identifierhttp://hdl.handle.net/10722/60688
ISSN
2015 Impact Factor: 3.297
2015 SCImago Journal Rankings: 1.936
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Government RGC7566/06M
7501/05M
Committee on Research and Conference Grants10205115
VA Merit Award
VA Research Career Scientist Award
NIHDK58411
DK076898
Funding Information:

This work was supported by the Hong Kong Government RGC grants (7566/06M, 7501/05M) and the Committee on Research and Conference Grants (10205115) to B. K. C. Chow, and a VA Merit Award, VA Research Career Scientist Award, and the NIH grant DK58411 and DK076898 to G. Alpini.

References

 

DC FieldValueLanguage
dc.contributor.authorLam, IPYen_HK
dc.contributor.authorLee, LTOen_HK
dc.contributor.authorChoi, HSen_HK
dc.contributor.authorAlpini, Gen_HK
dc.contributor.authorChow, BKCen_HK
dc.date.accessioned2010-05-31T04:16:32Z-
dc.date.available2010-05-31T04:16:32Z-
dc.date.issued2009en_HK
dc.identifier.citationAmerican Journal Of Physiology - Gastrointestinal And Liver Physiology, 2009, v. 297 n. 1, p. G90-G97en_HK
dc.identifier.issn0193-1857en_HK
dc.identifier.urihttp://hdl.handle.net/10722/60688-
dc.description.abstractSmall heterodimer partner (SHP) is an orphan nuclear receptor in which gene expression can be upregulated by bile acids. It regulates its target genes by repressing the transcriptional activities of other nuclear receptors including NeuroD, which has been shown to regulate secretin gene expression. Here, we evaluated the regulation on duodenal secretin gene expression by SHP and selected bile acids, cholic acid (CA) and chenodeoxycholic acid (CDCA). In vitro treatment of CDCA or fexaramine elevated the SHP transcript level and occupancy on secretin promoter. The increase in the SHP level, induced by bile acid treatment or overexpression, reduced secretin gene expression, whereas this gene inhibitory effect was reversed by silencing of endogenous SHP. In in vivo studies, double-immunofluorescence staining demonstrated the coexpression of secretin and SHP in mouse duodenum. Feeding mice with 1% CA-enriched rodent chow resulted in upregulation of SHP and a concomitant decrease in secretin transcript and protein levels in duodenum compared with the control group fed with normal chow. A diet enriched with 5% cholestyramine led to a decrease in SHP level and a corresponding increase in secretin expression. Overall, this study showed that bile acids via SHP inhibit duodenal secretin gene expression. Because secretin is a key hormone that stimulates bile flow in cholangiocytes, this pathway thus provides a novel means to modulate secretin-stimulated choleresis in response to intraduodenal bile acids. Copyright © 2009 the American Physiological Society.en_HK
dc.languageengen_HK
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpgi.physiology.org/en_HK
dc.relation.ispartofAmerican Journal of Physiology - Gastrointestinal and Liver Physiologyen_HK
dc.subjectBile flowen_HK
dc.subjectCholangiocyteen_HK
dc.subjectCholeresisen_HK
dc.subjectLiveren_HK
dc.titleBile acids inhibit duodenal secretin expression via orphan nuclear receptor small heterodimer partner (SHP)en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0193-1857&volume=&spage=297: G90&epage=G97&date=2009&atitle=Bile+Acids+Inhibit+Duodenal+Secretin+Expression+via+Orphan+Nuclear++Receptor+Small+Heterodimer+Partner+(SHP).en_HK
dc.identifier.emailLee, LTO: ltolee2@hkucc.hku.hken_HK
dc.identifier.emailChow, BKC: bkcc@hku.hken_HK
dc.identifier.authorityLee, LTO=rp00727en_HK
dc.identifier.authorityChow, BKC=rp00681en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1152/ajpgi.00094.2009en_HK
dc.identifier.pmid19372104-
dc.identifier.scopuseid_2-s2.0-67650088002en_HK
dc.identifier.hkuros157558en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-67650088002&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume297en_HK
dc.identifier.issue1en_HK
dc.identifier.spageG90en_HK
dc.identifier.epageG97en_HK
dc.identifier.isiWOS:000268150500011-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f10001160014-
dc.identifier.scopusauthoridLam, IPY=14050702700en_HK
dc.identifier.scopusauthoridLee, LTO=8367269000en_HK
dc.identifier.scopusauthoridChoi, HS=7404338771en_HK
dc.identifier.scopusauthoridAlpini, G=7005824212en_HK
dc.identifier.scopusauthoridChow, BKC=7102826193en_HK

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