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Article: Hepatic stellate cell-targeted delivery of M6P-HSA-glycyrrhetinic acid attenuates hepatic fibrogenesis in a bile duct ligation rat model

TitleHepatic stellate cell-targeted delivery of M6P-HSA-glycyrrhetinic acid attenuates hepatic fibrogenesis in a bile duct ligation rat model
Authors
KeywordsGlycyrrhetinic acid
Hepatic stellate cells
Liver fibrosis
M6P26-HSA
Type I collagen
Issue Date2007
PublisherWiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1478-3223&site=1
Citation
Liver International, 2007, v. 27 n. 4, p. 548-557 How to Cite?
AbstractBackground/Aims: Hepatic stellate cells (HSCs) play a key role in fibrogenesis. Here, we used mannose-6-phosphate-modified human serum albumin (M6P 26 -HSA) as a selective carrier to deliver antifibrotic drug 18β-glycyrrhetinic acid (18β-GA) in experimental fibrosis animals, and tested its effect in injured liver tissues. Methods: Bile duct ligation (BDL) was performed to induce liver damage in rats. Masson's stain and immunocytochemistry were used to assess hepatic collagen deposits and uptakes of M6P26-HSA-GA in HSCs in rat livers. Gene expression profiles of procollagen type I α2, smooth muscle actin (SMA), and transforming growth factor-β1 (TGF-β1) were analysed by TaqMan and quantitative polymerase chain reaction assays. The depositions of M6P26-HSA-GA in the HSC-T6 cell line and primary HSCs were assessed by immunofluorescent staining. Results: Treatment with M6P26-HSA-GA at 10 mg/kg (three times/week for 2 weeks), but not the equivalent doses of free 18β-GA and M6P26-HSA carrier alone, could significantly attenuate collagen deposits in BDL rat liver. Masson's stain and TaqMan assay revealed significant modulation of procollagen type I α2 in the BDL-injured liver. The depositions of M6P26-HSA-GA in HSCs were revealed by immunostaining with HSA and SMA markers. M6P26-HSA bound activated HSCs in vitro and the immunoreactivity of M6P26-HSA-GA was detected in the cytoplasm and cell surface of HSCs and HSC-T6 cells. The gene transcript levels of SMA and TGF-β1 were modulated in HSC-T6 cells treated with M6P26-HSA-GA. Conclusions: The M6P26-HSA holds promise as a targeting carrier for the liver or HSCs, which may be used to deliver 18β-GA as a therapeutic agent to treat liver fibrosis. © 2007 Blackwell Munksgaard.
Persistent Identifierhttp://hdl.handle.net/10722/83366
ISSN
2015 Impact Factor: 4.47
2015 SCImago Journal Rankings: 1.677
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLuk, JMen_HK
dc.contributor.authorZhang, QSen_HK
dc.contributor.authorLee, NPen_HK
dc.contributor.authorWo, JYen_HK
dc.contributor.authorLeung, PPen_HK
dc.contributor.authorLiu, LXen_HK
dc.contributor.authorHu, MYen_HK
dc.contributor.authorCheung, KFen_HK
dc.contributor.authorHui, CKen_HK
dc.contributor.authorLau, GKen_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2010-09-06T08:40:10Z-
dc.date.available2010-09-06T08:40:10Z-
dc.date.issued2007en_HK
dc.identifier.citationLiver International, 2007, v. 27 n. 4, p. 548-557en_HK
dc.identifier.issn1478-3223en_HK
dc.identifier.urihttp://hdl.handle.net/10722/83366-
dc.description.abstractBackground/Aims: Hepatic stellate cells (HSCs) play a key role in fibrogenesis. Here, we used mannose-6-phosphate-modified human serum albumin (M6P 26 -HSA) as a selective carrier to deliver antifibrotic drug 18β-glycyrrhetinic acid (18β-GA) in experimental fibrosis animals, and tested its effect in injured liver tissues. Methods: Bile duct ligation (BDL) was performed to induce liver damage in rats. Masson's stain and immunocytochemistry were used to assess hepatic collagen deposits and uptakes of M6P26-HSA-GA in HSCs in rat livers. Gene expression profiles of procollagen type I α2, smooth muscle actin (SMA), and transforming growth factor-β1 (TGF-β1) were analysed by TaqMan and quantitative polymerase chain reaction assays. The depositions of M6P26-HSA-GA in the HSC-T6 cell line and primary HSCs were assessed by immunofluorescent staining. Results: Treatment with M6P26-HSA-GA at 10 mg/kg (three times/week for 2 weeks), but not the equivalent doses of free 18β-GA and M6P26-HSA carrier alone, could significantly attenuate collagen deposits in BDL rat liver. Masson's stain and TaqMan assay revealed significant modulation of procollagen type I α2 in the BDL-injured liver. The depositions of M6P26-HSA-GA in HSCs were revealed by immunostaining with HSA and SMA markers. M6P26-HSA bound activated HSCs in vitro and the immunoreactivity of M6P26-HSA-GA was detected in the cytoplasm and cell surface of HSCs and HSC-T6 cells. The gene transcript levels of SMA and TGF-β1 were modulated in HSC-T6 cells treated with M6P26-HSA-GA. Conclusions: The M6P26-HSA holds promise as a targeting carrier for the liver or HSCs, which may be used to deliver 18β-GA as a therapeutic agent to treat liver fibrosis. © 2007 Blackwell Munksgaard.en_HK
dc.languageengen_HK
dc.publisherWiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1478-3223&site=1en_HK
dc.relation.ispartofLiver Internationalen_HK
dc.subjectGlycyrrhetinic aciden_HK
dc.subjectHepatic stellate cellsen_HK
dc.subjectLiver fibrosisen_HK
dc.subjectM6P26-HSAen_HK
dc.subjectType I collagenen_HK
dc.titleHepatic stellate cell-targeted delivery of M6P-HSA-glycyrrhetinic acid attenuates hepatic fibrogenesis in a bile duct ligation rat modelen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1478-3223&volume=27&issue=4&spage=548&epage=557&date=2007&atitle=Hepatic+stellate+cell-targeted+delivery+of+M6P-HSA-glycyrrhetinic+acid+attenuates+hepatic+fibrogenesis+in+a+bile+duct+ligation+rat+modelen_HK
dc.identifier.emailLuk, JM: jmluk@hkucc.hku.hken_HK
dc.identifier.emailLee, NP: nikkilee@hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityLuk, JM=rp00349en_HK
dc.identifier.authorityLee, NP=rp00263en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1478-3231.2007.01452.xen_HK
dc.identifier.pmid17403195-
dc.identifier.scopuseid_2-s2.0-34047200700en_HK
dc.identifier.hkuros126592en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34047200700&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume27en_HK
dc.identifier.issue4en_HK
dc.identifier.spage548en_HK
dc.identifier.epage557en_HK
dc.identifier.isiWOS:000245412900015-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLuk, JM=7006777791en_HK
dc.identifier.scopusauthoridZhang, QS=7406720236en_HK
dc.identifier.scopusauthoridLee, NP=7402722690en_HK
dc.identifier.scopusauthoridWo, JY=7003466728en_HK
dc.identifier.scopusauthoridLeung, PP=7401749062en_HK
dc.identifier.scopusauthoridLiu, LX=13611939300en_HK
dc.identifier.scopusauthoridHu, MY=7402639252en_HK
dc.identifier.scopusauthoridCheung, KF=8763216400en_HK
dc.identifier.scopusauthoridHui, CK=7202876933en_HK
dc.identifier.scopusauthoridLau, GK=7102301257en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK
dc.identifier.citeulike1210385-

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