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Article: Adenosine-5'-triphosphate up-regulates proliferation of human cardiac fibroblasts

TitleAdenosine-5'-triphosphate up-regulates proliferation of human cardiac fibroblasts
Authors
KeywordsATP
cardiac fibroblasts
cell cycling
cell migration
proliferation
Issue Date2012
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1
Citation
British Journal Of Pharmacology, 2012, v. 166 n. 3, p. 1140-1150 How to Cite?
AbstractBackground and Purpose ATP is a potent signalling molecule that regulates biological activities including increasing or decreasing proliferation in different types of cells. The aim of the present study was to investigate how ATP regulates the proliferation of human cardiac fibroblasts. EXPERIMENTAL APPROACH Reverse transcription (RT)-PCR, Western blot analysis, cell proliferation and migration assays were employed to investigate the effects of ATP on human adult ventricular fibroblasts. Key Results ATP increased cell proliferation in a concentration-dependent manner. Similarly, the P2X receptor agonist α,β-methylene ATP and P2Y receptor agonist ATP-γS also up-regulated cell proliferation. The P2 receptor antagonists suramin and reactive blue-2 prevented the ATP-induced increase in proliferation and RT-PCR and Western blot analysis revealed that mRNAs of P2X 4/7 and P2Y 2 are abundant in cardiac fibroblasts. ATP increased phosphorylated PKB (Akt) and ERK1/2 levels; an effect antagonized by suramin, reactive blue-2, the PI3-kinase inhibitor, wortmannin, PKB inhibitor, API-2, and MAPK inhibitor, PD98059. These kinase inhibitors also prevented the ATP-induced increase in proliferation. In addition, ATP enhanced the progression of cells from the G0/G1 phase to the S phase by increasing the expression of proteins for cyclin D1 and cyclin E. Silencing the P2X 4/7 and P2Y 2 receptors with siRNA targeting the corresponding receptor diminished ATP-stimulated proliferation and migration of the cardiac fibroblasts. Conclusion and Implication ATP activates P2X 4/7 and P2Y 2 receptors and up-regulates the proliferation of human cardiac fibroblasts by promoting cell cycling progression. It also increases the migration of these cells. These effects of ATP may be involved in cardiac remodelling of injured hearts. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
Persistent Identifierhttp://hdl.handle.net/10722/144560
ISSN
2014 Impact Factor: 4.842
2013 SCImago Journal Rankings: 2.253
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council of Hong KongHKU 770108 M
University of Hong Kong
Funding Information:

The study was supported by a General Research Fund (HKU 770108 M) from Research Grant Council of Hong Kong. J-BC was supported by a postgraduate studentship from the University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorChen, JBen_HK
dc.contributor.authorLiu, WJen_HK
dc.contributor.authorChe, Hen_HK
dc.contributor.authorLiu, Jen_HK
dc.contributor.authorSun, HYen_HK
dc.contributor.authorLi, GRen_HK
dc.date.accessioned2012-02-03T06:13:43Z-
dc.date.available2012-02-03T06:13:43Z-
dc.date.issued2012en_HK
dc.identifier.citationBritish Journal Of Pharmacology, 2012, v. 166 n. 3, p. 1140-1150en_HK
dc.identifier.issn0007-1188en_HK
dc.identifier.urihttp://hdl.handle.net/10722/144560-
dc.description.abstractBackground and Purpose ATP is a potent signalling molecule that regulates biological activities including increasing or decreasing proliferation in different types of cells. The aim of the present study was to investigate how ATP regulates the proliferation of human cardiac fibroblasts. EXPERIMENTAL APPROACH Reverse transcription (RT)-PCR, Western blot analysis, cell proliferation and migration assays were employed to investigate the effects of ATP on human adult ventricular fibroblasts. Key Results ATP increased cell proliferation in a concentration-dependent manner. Similarly, the P2X receptor agonist α,β-methylene ATP and P2Y receptor agonist ATP-γS also up-regulated cell proliferation. The P2 receptor antagonists suramin and reactive blue-2 prevented the ATP-induced increase in proliferation and RT-PCR and Western blot analysis revealed that mRNAs of P2X 4/7 and P2Y 2 are abundant in cardiac fibroblasts. ATP increased phosphorylated PKB (Akt) and ERK1/2 levels; an effect antagonized by suramin, reactive blue-2, the PI3-kinase inhibitor, wortmannin, PKB inhibitor, API-2, and MAPK inhibitor, PD98059. These kinase inhibitors also prevented the ATP-induced increase in proliferation. In addition, ATP enhanced the progression of cells from the G0/G1 phase to the S phase by increasing the expression of proteins for cyclin D1 and cyclin E. Silencing the P2X 4/7 and P2Y 2 receptors with siRNA targeting the corresponding receptor diminished ATP-stimulated proliferation and migration of the cardiac fibroblasts. Conclusion and Implication ATP activates P2X 4/7 and P2Y 2 receptors and up-regulates the proliferation of human cardiac fibroblasts by promoting cell cycling progression. It also increases the migration of these cells. These effects of ATP may be involved in cardiac remodelling of injured hearts. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.en_HK
dc.languageengen_US
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1en_HK
dc.relation.ispartofBritish Journal of Pharmacologyen_HK
dc.rightsBritish Journal of Pharmacology. Copyright © John Wiley & Sons Ltd.-
dc.subjectATPen_HK
dc.subjectcardiac fibroblastsen_HK
dc.subjectcell cyclingen_HK
dc.subjectcell migrationen_HK
dc.subjectproliferationen_HK
dc.titleAdenosine-5'-triphosphate up-regulates proliferation of human cardiac fibroblastsen_HK
dc.typeArticleen_HK
dc.identifier.emailLi, GR:grli@hkucc.hku.hken_HK
dc.identifier.authorityLi, GR=rp00476en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1476-5381.2012.01831.xen_HK
dc.identifier.pmid22224416-
dc.identifier.scopuseid_2-s2.0-84860843028en_HK
dc.identifier.hkuros198541en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84860843028&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume166en_HK
dc.identifier.issue3en_HK
dc.identifier.spage1140en_HK
dc.identifier.epage1150en_HK
dc.identifier.isiWOS:000303923000026-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridChen, JB=35213097600en_HK
dc.identifier.scopusauthoridLiu, WJ=54380301800en_HK
dc.identifier.scopusauthoridChe, H=55214759400en_HK
dc.identifier.scopusauthoridLiu, J=55078014900en_HK
dc.identifier.scopusauthoridSun, HY=53265070800en_HK
dc.identifier.scopusauthoridLi, GR=7408462932en_HK

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