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Article: Adenosine-5'-triphosphate up-regulates proliferation of human cardiac fibroblasts
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TitleAdenosine-5'-triphosphate up-regulates proliferation of human cardiac fibroblasts
 
AuthorsChen, JB2
Liu, WJ2
Che, H2
Liu, J1
Sun, HY2
Li, GR2
 
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
 
CitationBritish Journal Of Pharmacology, 2012, v. 166 n. 3, p. 1140-1150 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1476-5381.2012.01831.x
 
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.
 
ISSN0007-1188
2013 Impact Factor: 4.990
2013 SCImago Journal Rankings: 2.253
 
DOIhttp://dx.doi.org/10.1111/j.1476-5381.2012.01831.x
 
ISI Accession Number IDWOS:000303923000026
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.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorChen, JB
 
dc.contributor.authorLiu, WJ
 
dc.contributor.authorChe, H
 
dc.contributor.authorLiu, J
 
dc.contributor.authorSun, HY
 
dc.contributor.authorLi, GR
 
dc.date.accessioned2012-02-03T06:13:43Z
 
dc.date.available2012-02-03T06:13:43Z
 
dc.date.issued2012
 
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.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationBritish Journal Of Pharmacology, 2012, v. 166 n. 3, p. 1140-1150 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1476-5381.2012.01831.x
 
dc.identifier.doihttp://dx.doi.org/10.1111/j.1476-5381.2012.01831.x
 
dc.identifier.epage1150
 
dc.identifier.hkuros198541
 
dc.identifier.isiWOS:000303923000026
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.

 
dc.identifier.issn0007-1188
2013 Impact Factor: 4.990
2013 SCImago Journal Rankings: 2.253
 
dc.identifier.issue3
 
dc.identifier.pmid22224416
 
dc.identifier.scopuseid_2-s2.0-84860843028
 
dc.identifier.spage1140
 
dc.identifier.urihttp://hdl.handle.net/10722/144560
 
dc.identifier.volume166
 
dc.languageeng
 
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofBritish Journal of Pharmacology
 
dc.relation.referencesReferences in Scopus
 
dc.rightsBritish Journal of Pharmacology. Copyright © John Wiley & Sons Ltd.
 
dc.subjectATP
 
dc.subjectcardiac fibroblasts
 
dc.subjectcell cycling
 
dc.subjectcell migration
 
dc.subjectproliferation
 
dc.titleAdenosine-5'-triphosphate up-regulates proliferation of human cardiac fibroblasts
 
dc.typeArticle
 
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<contributor.author>Li, GR</contributor.author>
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Author Affiliations
  1. Shenzhen University
  2. The University of Hong Kong Li Ka Shing Faculty of Medicine