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Article: Adrenomedullin Enhances Invasion of Human Extravillous Cytotrophoblast-Derived Cell Lines by Regulation of Urokinase Plasminogen Activator Expression and S-Nitrosylation

TitleAdrenomedullin Enhances Invasion of Human Extravillous Cytotrophoblast-Derived Cell Lines by Regulation of Urokinase Plasminogen Activator Expression and S-Nitrosylation
Authors
KeywordsAdrenomedullin
Human extravillous cytotrophoblast
Invasion
Nitric oxide
Urokinase plasminogen activator
Issue Date2013
PublisherSociety for the Study of Reproduction. The Journal's web site is located at http://www.biolreprod.org/
Citation
Biology of Reproduction, 2013, v. 88 n. 2, article no. 34 How to Cite?
AbstractExtravillous cytotrophoblast (EVCT) is responsible for trophoblast invasion, which is an important process during placentation. Dysregulation of the process is associated with a wide range of pregnancy complications. Adrenomedullin (ADM) is a polypeptide expressed most abundantly in first-trimester placentas. We hypothesized that ADM modulated the invasion of human EVCT. Our results showed that ADM enhanced invasion and migration but not proliferation in two EVCT cell lines, JEG-3 and TEV-1. Similar observation can also be obtained in primary EVCTs. JEG-3 and TEV-1 cells expressed ADM receptor components as demonstrated by immunostaining, Western blotting, and RT-PCR. The ADM antagonist ADM22–52 (ADM C-terminal 22-52 amino acid fragment) suppressed ADM-induced invasion and migration, confirming that ADM exerted its biological effects through its classical receptors. The stimulatory effect of ADM on EVCT invasiveness was associated with induction (P < 0.05) of urokinase plasminogen activator (uPA) and nitric oxide synthase (NOS) expression and activity. Silencing of uPA by siRNA transfection abolished the stimulatory effect of ADM, suggesting that uPA is the key mediator for ADM-induced invasion. The involvement of NO in enhancing the invasion and biosynthesis of uPA in EVCT cell lines was confirmed by using pharmacological inhibitors of NOS and NO donors. ADM-mediated NO production also increased protein S-nitrosylation of JEG-3 cells. S-nitrosylation activated uPA in vitro and induced a higher proteinase activity. These findings provide indications that ADM and its downstream NO signaling may play an important role in modulating human EVCT functions.
DescriptionSupported by funding from the University of Hong Kong (code 104106)
Persistent Identifierhttp://hdl.handle.net/10722/197986
ISSN
2015 Impact Factor: 3.471
2015 SCImago Journal Rankings: 1.646
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWong, BST-
dc.contributor.authorLam, KKW-
dc.contributor.authorLee, CL-
dc.contributor.authorWong, VHH-
dc.contributor.authorLam, MPY-
dc.contributor.authorChu, IK-
dc.contributor.authorYeung, WSB-
dc.contributor.authorChiu, PCN-
dc.date.accessioned2014-06-20T06:45:03Z-
dc.date.available2014-06-20T06:45:03Z-
dc.date.issued2013-
dc.identifier.citationBiology of Reproduction, 2013, v. 88 n. 2, article no. 34-
dc.identifier.issn0006-3363-
dc.identifier.urihttp://hdl.handle.net/10722/197986-
dc.descriptionSupported by funding from the University of Hong Kong (code 104106)-
dc.description.abstractExtravillous cytotrophoblast (EVCT) is responsible for trophoblast invasion, which is an important process during placentation. Dysregulation of the process is associated with a wide range of pregnancy complications. Adrenomedullin (ADM) is a polypeptide expressed most abundantly in first-trimester placentas. We hypothesized that ADM modulated the invasion of human EVCT. Our results showed that ADM enhanced invasion and migration but not proliferation in two EVCT cell lines, JEG-3 and TEV-1. Similar observation can also be obtained in primary EVCTs. JEG-3 and TEV-1 cells expressed ADM receptor components as demonstrated by immunostaining, Western blotting, and RT-PCR. The ADM antagonist ADM22–52 (ADM C-terminal 22-52 amino acid fragment) suppressed ADM-induced invasion and migration, confirming that ADM exerted its biological effects through its classical receptors. The stimulatory effect of ADM on EVCT invasiveness was associated with induction (P < 0.05) of urokinase plasminogen activator (uPA) and nitric oxide synthase (NOS) expression and activity. Silencing of uPA by siRNA transfection abolished the stimulatory effect of ADM, suggesting that uPA is the key mediator for ADM-induced invasion. The involvement of NO in enhancing the invasion and biosynthesis of uPA in EVCT cell lines was confirmed by using pharmacological inhibitors of NOS and NO donors. ADM-mediated NO production also increased protein S-nitrosylation of JEG-3 cells. S-nitrosylation activated uPA in vitro and induced a higher proteinase activity. These findings provide indications that ADM and its downstream NO signaling may play an important role in modulating human EVCT functions.-
dc.languageeng-
dc.publisherSociety for the Study of Reproduction. The Journal's web site is located at http://www.biolreprod.org/-
dc.relation.ispartofBiology of Reproduction-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectAdrenomedullin-
dc.subjectHuman extravillous cytotrophoblast-
dc.subjectInvasion-
dc.subjectNitric oxide-
dc.subjectUrokinase plasminogen activator-
dc.titleAdrenomedullin Enhances Invasion of Human Extravillous Cytotrophoblast-Derived Cell Lines by Regulation of Urokinase Plasminogen Activator Expression and S-Nitrosylationen_US
dc.typeArticleen_US
dc.identifier.emailLam, KKW: kawai7@hkucc.hku.hk-
dc.identifier.emailLee, CL: kcllee@hku.hk-
dc.identifier.emailYeung, WSB: wsbyeung@hkucc.hku.hk-
dc.identifier.emailChiu, PCN: pchiucn@hku.hk-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1095/biolreprod.112.103903-
dc.identifier.pmid23242529-
dc.identifier.scopuseid_2-s2.0-84877028183-
dc.identifier.hkuros238663-
dc.identifier.hkuros238670-
dc.identifier.volume88-
dc.identifier.issue2-
dc.identifier.isiWOS:000314925300006-
dc.publisher.placeUnited States-

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