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- Publisher Website: 10.1152/ajpgi.00094.2009
- Scopus: eid_2-s2.0-67650088002
- PMID: 19372104
- WOS: WOS:000268150500011
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Article: Bile acids inhibit duodenal secretin expression via orphan nuclear receptor small heterodimer partner (SHP)
Title | Bile acids inhibit duodenal secretin expression via orphan nuclear receptor small heterodimer partner (SHP) | ||||||||||||
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Authors | |||||||||||||
Keywords | Bile flow Cholangiocyte Choleresis Liver | ||||||||||||
Issue Date | 2009 | ||||||||||||
Publisher | American 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? | ||||||||||||
Abstract | Small 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 Identifier | http://hdl.handle.net/10722/60688 | ||||||||||||
ISSN | 2023 Impact Factor: 3.9 2023 SCImago Journal Rankings: 1.460 | ||||||||||||
ISI Accession Number ID |
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 Field | Value | Language |
---|---|---|
dc.contributor.author | Lam, IPY | en_HK |
dc.contributor.author | Lee, LTO | en_HK |
dc.contributor.author | Choi, HS | en_HK |
dc.contributor.author | Alpini, G | en_HK |
dc.contributor.author | Chow, BKC | en_HK |
dc.date.accessioned | 2010-05-31T04:16:32Z | - |
dc.date.available | 2010-05-31T04:16:32Z | - |
dc.date.issued | 2009 | en_HK |
dc.identifier.citation | American Journal Of Physiology - Gastrointestinal And Liver Physiology, 2009, v. 297 n. 1, p. G90-G97 | en_HK |
dc.identifier.issn | 0193-1857 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/60688 | - |
dc.description.abstract | Small 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.language | eng | en_HK |
dc.publisher | American Physiological Society. The Journal's web site is located at http://intl-ajpgi.physiology.org/ | en_HK |
dc.relation.ispartof | American Journal of Physiology - Gastrointestinal and Liver Physiology | en_HK |
dc.subject | Bile flow | en_HK |
dc.subject | Cholangiocyte | en_HK |
dc.subject | Choleresis | en_HK |
dc.subject | Liver | en_HK |
dc.title | Bile acids inhibit duodenal secretin expression via orphan nuclear receptor small heterodimer partner (SHP) | en_HK |
dc.type | Article | en_HK |
dc.identifier.openurl | http://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.email | Lee, LTO: ltolee2@hkucc.hku.hk | en_HK |
dc.identifier.email | Chow, BKC: bkcc@hku.hk | en_HK |
dc.identifier.authority | Lee, LTO=rp00727 | en_HK |
dc.identifier.authority | Chow, BKC=rp00681 | en_HK |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1152/ajpgi.00094.2009 | en_HK |
dc.identifier.pmid | 19372104 | - |
dc.identifier.scopus | eid_2-s2.0-67650088002 | en_HK |
dc.identifier.hkuros | 157558 | en_HK |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-67650088002&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 297 | en_HK |
dc.identifier.issue | 1 | en_HK |
dc.identifier.spage | G90 | en_HK |
dc.identifier.epage | G97 | en_HK |
dc.identifier.isi | WOS:000268150500011 | - |
dc.publisher.place | United States | en_HK |
dc.identifier.f1000 | 1160014 | - |
dc.identifier.scopusauthorid | Lam, IPY=14050702700 | en_HK |
dc.identifier.scopusauthorid | Lee, LTO=8367269000 | en_HK |
dc.identifier.scopusauthorid | Choi, HS=7404338771 | en_HK |
dc.identifier.scopusauthorid | Alpini, G=7005824212 | en_HK |
dc.identifier.scopusauthorid | Chow, BKC=7102826193 | en_HK |
dc.identifier.issnl | 0193-1857 | - |