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Article: Adeno-associated virus-mediated pancreatic and duodenal homeobox gene-1 expression enhanced differentiation of hepatic oval stem cells to insulin-producing cells in diabetic rats

TitleAdeno-associated virus-mediated pancreatic and duodenal homeobox gene-1 expression enhanced differentiation of hepatic oval stem cells to insulin-producing cells in diabetic rats
Authors
Issue Date2008
PublisherSpringer Verlag Dordrecht. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=1021-7770
Citation
Journal Of Biomedical Science, 2008, v. 15 n. 4, p. 487-497 How to Cite?
AbstractInducing autologous liver cells to differentiate into endocrine β cell has been a potential strategy for the treatment of type 1diabetes. However it is still not known which sub-population cells in the liver was responsible for this developmental shift. Pancreatic and duodenal homeobox gene 1 (pdx-1), a crucial transcription factor in pancreatic islet development and differentiation, has attracted much interests in beta cell differentiation experiments. This study was conducted to evaluate whether pdx-1 gene delivered by adeno-associated virus (AAV) could induce autologous liver cells to differentiate into insulin-producing cells and to explore the origin of these cells. Here we used 4 × 10e11 AAV to deliver pdx-1 to STZ-induced diabetic rats via the portal vein. Immunofluorescent staining showed more insulin-positive cells, which had similar morphology with hepatic oval stem cells and were positive for hepatic oval stem cell markers, Thy-1 and cytokeratin 19 (ck19). In addition to the expression of pdx-1, insulin1 and insulin2, RT-PCR and quantitative real-time PCR also detected significantly higher levels of other important transcription factors in AAV-pdx-1 treated diabetic rat livers. AAV-pdx-1 treated diabetic rats showed partially ameliorated hyperglycemia, better gain of body weight and improved lipid levels. Our data indicated that rat hepatic oval stem cells were differentiated into bioactive insulin-producing cells by AAV-pdx-1 delivery in diabetic rats, with promoted expression of some transcription factors necessary for beta cell development and function. © 2008 National Science Council.
Persistent Identifierhttp://hdl.handle.net/10722/77303
ISSN
2015 Impact Factor: 2.935
2015 SCImago Journal Rankings: 1.280
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, Hen_HK
dc.contributor.authorLi, Xen_HK
dc.contributor.authorLam, KSLen_HK
dc.contributor.authorTam, Sen_HK
dc.contributor.authorXiao, Wen_HK
dc.contributor.authorXu, Ren_HK
dc.date.accessioned2010-09-06T07:30:26Z-
dc.date.available2010-09-06T07:30:26Z-
dc.date.issued2008en_HK
dc.identifier.citationJournal Of Biomedical Science, 2008, v. 15 n. 4, p. 487-497en_HK
dc.identifier.issn1021-7770en_HK
dc.identifier.urihttp://hdl.handle.net/10722/77303-
dc.description.abstractInducing autologous liver cells to differentiate into endocrine β cell has been a potential strategy for the treatment of type 1diabetes. However it is still not known which sub-population cells in the liver was responsible for this developmental shift. Pancreatic and duodenal homeobox gene 1 (pdx-1), a crucial transcription factor in pancreatic islet development and differentiation, has attracted much interests in beta cell differentiation experiments. This study was conducted to evaluate whether pdx-1 gene delivered by adeno-associated virus (AAV) could induce autologous liver cells to differentiate into insulin-producing cells and to explore the origin of these cells. Here we used 4 × 10e11 AAV to deliver pdx-1 to STZ-induced diabetic rats via the portal vein. Immunofluorescent staining showed more insulin-positive cells, which had similar morphology with hepatic oval stem cells and were positive for hepatic oval stem cell markers, Thy-1 and cytokeratin 19 (ck19). In addition to the expression of pdx-1, insulin1 and insulin2, RT-PCR and quantitative real-time PCR also detected significantly higher levels of other important transcription factors in AAV-pdx-1 treated diabetic rat livers. AAV-pdx-1 treated diabetic rats showed partially ameliorated hyperglycemia, better gain of body weight and improved lipid levels. Our data indicated that rat hepatic oval stem cells were differentiated into bioactive insulin-producing cells by AAV-pdx-1 delivery in diabetic rats, with promoted expression of some transcription factors necessary for beta cell development and function. © 2008 National Science Council.en_HK
dc.languageengen_HK
dc.publisherSpringer Verlag Dordrecht. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=1021-7770en_HK
dc.relation.ispartofJournal of Biomedical Scienceen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshBiological Markers - analysisen_HK
dc.subject.meshBody Weighten_HK
dc.subject.meshCell Differentiationen_HK
dc.subject.meshDependovirus - geneticsen_HK
dc.subject.meshDiabetes Mellitus, Experimental - therapyen_HK
dc.subject.meshDuodenum - metabolismen_HK
dc.subject.meshGene Therapyen_HK
dc.subject.meshGenes, Homeobox - geneticsen_HK
dc.subject.meshGenetic Vectorsen_HK
dc.subject.meshHepatocytes - cytologyen_HK
dc.subject.meshHyperglycemiaen_HK
dc.subject.meshInsulin-Secreting Cells - cytologyen_HK
dc.subject.meshLipid Metabolismen_HK
dc.subject.meshMaleen_HK
dc.subject.meshPancreas - metabolismen_HK
dc.subject.meshRatsen_HK
dc.subject.meshRats, Sprague-Dawleyen_HK
dc.subject.meshStem Cells - cytologyen_HK
dc.subject.meshTranscription Factors - geneticsen_HK
dc.subject.meshTreatment Outcomeen_HK
dc.titleAdeno-associated virus-mediated pancreatic and duodenal homeobox gene-1 expression enhanced differentiation of hepatic oval stem cells to insulin-producing cells in diabetic ratsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1021-7770&volume=&spage=&epage=&date=2008&atitle=Adeno-associated+virus-mediated+pancreatic+and+duodenal+homeobox+gene-1+expression+enhanced+differentiation+of+hepatic+oval+stem+cells+to+insulin-producing+cells+in+diabetic+ratsen_HK
dc.identifier.emailLam, KSL:ksllam@hku.hken_HK
dc.identifier.authorityLam, KSL=rp00343en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s11373-008-9233-3en_HK
dc.identifier.pmid18253862-
dc.identifier.scopuseid_2-s2.0-44949159838en_HK
dc.identifier.hkuros142249en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-44949159838&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume15en_HK
dc.identifier.issue4en_HK
dc.identifier.spage487en_HK
dc.identifier.epage497en_HK
dc.identifier.isiWOS:000256471900006-
dc.publisher.placeNetherlandsen_HK
dc.identifier.scopusauthoridLi, H=36078286800en_HK
dc.identifier.scopusauthoridLi, X=23497242700en_HK
dc.identifier.scopusauthoridLam, KSL=8082870600en_HK
dc.identifier.scopusauthoridTam, S=7202037323en_HK
dc.identifier.scopusauthoridXiao, W=7202456485en_HK
dc.identifier.scopusauthoridXu, R=16426308500en_HK
dc.identifier.citeulike6464775-

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