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Article: TNP-470 blockage of VEGF synthesis is dependent on MAPK/COX-2 signaling pathway in PDGF-BB-activated hepatic stellate cells

TitleTNP-470 blockage of VEGF synthesis is dependent on MAPK/COX-2 signaling pathway in PDGF-BB-activated hepatic stellate cells
Authors
KeywordsActivated hepatic stellate cells
Angiogenesis
COX-2
PDGF-BB
TNP-470
VEGF
Issue Date2006
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/wps/find/journaldescription.cws_home/622790/description
Citation
Biochemical And Biophysical Research Communications, 2006, v. 341 n. 1, p. 239-244 How to Cite?
AbstractAngiogenesis is a key pathogenic event in hepatic fibrogenesis, which is mediated by activated hepatic stellate cells (HSCs). TNP-470 is a known anti-angiogenic agent in cancer, and in this study, we investigated the regulatory mechanisms of TNP-470 blockage of vascular endothelial growth factor (VEGF) synthesis in activated HSCs. Primary HSCs were isolated from rat liver, cultured in vitro, and activated with platelet-derived growth factor-BB (PDGF-BB). After treatment with TNP-470, Nimesulide, PD98059, SB203580 or SP600125, activated HSCs were analyzed by immunoblotting, quantitative RT-PCR, and ELISA for mitogen-activated protein kinase (MAPK) family [ERKs, JNK, and p38], cyclooxygenase-2 (COX-2), and VEGF levels. Phosphorylation of p44/42 MAPK, which was followed by increased expressions of COX-2 and VEGF, was observed in PDGF-BB-activated HSCs; these events could be ameliorated by addition with TNP-470 in time- and dose-dependent manners. TNP-470 also inhibited the secretion of VEGF from activated HSCs into culture supernatant. Furthermore, TNP-470 blockage of VEGF production in activated HSCs could be nullified by exogenous inoculation with prostaglandin E2. In summary, our findings suggest that TNP-470 exhibits the observed anti-angiogenic properties in activated HSCs by targeting the COX-2/phospho-p44/42 MAPK pathway to inhibit VEGF production. © 2006 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/84024
ISSN
2015 Impact Factor: 2.371
2015 SCImago Journal Rankings: 1.152
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWang, YQen_HK
dc.contributor.authorLuk, JMen_HK
dc.contributor.authorChu, ACen_HK
dc.contributor.authorIkeda, Ken_HK
dc.contributor.authorMan, Ken_HK
dc.contributor.authorKaneda, Ken_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2010-09-06T08:48:01Z-
dc.date.available2010-09-06T08:48:01Z-
dc.date.issued2006en_HK
dc.identifier.citationBiochemical And Biophysical Research Communications, 2006, v. 341 n. 1, p. 239-244en_HK
dc.identifier.issn0006-291Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/84024-
dc.description.abstractAngiogenesis is a key pathogenic event in hepatic fibrogenesis, which is mediated by activated hepatic stellate cells (HSCs). TNP-470 is a known anti-angiogenic agent in cancer, and in this study, we investigated the regulatory mechanisms of TNP-470 blockage of vascular endothelial growth factor (VEGF) synthesis in activated HSCs. Primary HSCs were isolated from rat liver, cultured in vitro, and activated with platelet-derived growth factor-BB (PDGF-BB). After treatment with TNP-470, Nimesulide, PD98059, SB203580 or SP600125, activated HSCs were analyzed by immunoblotting, quantitative RT-PCR, and ELISA for mitogen-activated protein kinase (MAPK) family [ERKs, JNK, and p38], cyclooxygenase-2 (COX-2), and VEGF levels. Phosphorylation of p44/42 MAPK, which was followed by increased expressions of COX-2 and VEGF, was observed in PDGF-BB-activated HSCs; these events could be ameliorated by addition with TNP-470 in time- and dose-dependent manners. TNP-470 also inhibited the secretion of VEGF from activated HSCs into culture supernatant. Furthermore, TNP-470 blockage of VEGF production in activated HSCs could be nullified by exogenous inoculation with prostaglandin E2. In summary, our findings suggest that TNP-470 exhibits the observed anti-angiogenic properties in activated HSCs by targeting the COX-2/phospho-p44/42 MAPK pathway to inhibit VEGF production. © 2006 Elsevier Inc. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/wps/find/journaldescription.cws_home/622790/descriptionen_HK
dc.relation.ispartofBiochemical and Biophysical Research Communicationsen_HK
dc.subjectActivated hepatic stellate cellsen_HK
dc.subjectAngiogenesisen_HK
dc.subjectCOX-2en_HK
dc.subjectPDGF-BBen_HK
dc.subjectTNP-470en_HK
dc.subjectVEGFen_HK
dc.titleTNP-470 blockage of VEGF synthesis is dependent on MAPK/COX-2 signaling pathway in PDGF-BB-activated hepatic stellate cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0006-291X&volume=341-&issue=1&spage=239&epage=244 (corresponding author)&date=2006&atitle=TNP-470+blockage+of+VEGF+synthesis+is+dependent+on+MAPK/COX-2+signaling+pathway+in+PDGF-BB-activated+hepatic+stellate+cellsen_HK
dc.identifier.emailLuk, JM: jmluk@hkucc.hku.hken_HK
dc.identifier.emailChu, AC: bcccy@hkucc.hku.hken_HK
dc.identifier.emailMan, K: kwanman@hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityLuk, JM=rp00349en_HK
dc.identifier.authorityChu, AC=rp00505en_HK
dc.identifier.authorityMan, K=rp00417en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.bbrc.2005.12.175en_HK
dc.identifier.pmid16413500-
dc.identifier.scopuseid_2-s2.0-30944448391en_HK
dc.identifier.hkuros116895en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-30944448391&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume341en_HK
dc.identifier.issue1en_HK
dc.identifier.spage239en_HK
dc.identifier.epage244en_HK
dc.identifier.isiWOS:000235313400035-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridWang, YQ=23981317400en_HK
dc.identifier.scopusauthoridLuk, JM=7006777791en_HK
dc.identifier.scopusauthoridChu, AC=24343085700en_HK
dc.identifier.scopusauthoridIkeda, K=7404890758en_HK
dc.identifier.scopusauthoridMan, K=7101754072en_HK
dc.identifier.scopusauthoridKaneda, K=7202540217en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK

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