Article: Adenosine-5'-triphosphate up-regulates proliferation of human cardiac fibroblasts
| Title | Adenosine-5'-triphosphate up-regulates proliferation of human cardiac fibroblasts | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Chen, JB2 Liu, WJ2 Che, H2 Liu, J1 Sun, HY2 Li, GR2 | ||||||
| Keywords | ATP cardiac fibroblasts cell cycling cell migration proliferation | ||||||
| Issue Date | 2012 | ||||||
| Publisher | John 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?] DOI: http://dx.doi.org/10.1111/j.1476-5381.2012.01831.x | ||||||
| Abstract | Background 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. | ||||||
| ISSN | 0007-1188 2011 Impact Factor: 4.409 2011 SCImago Journal Rankings: 0.406 | ||||||
| DOI | http://dx.doi.org/10.1111/j.1476-5381.2012.01831.x | ||||||
| ISI Accession Number ID | WOS:000303923000026
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 | References in Scopus |
| dc.contributor.author | Chen, JB | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Liu, WJ | ||||||
| dc.contributor.author | Che, H | ||||||
| dc.contributor.author | Liu, J | ||||||
| dc.contributor.author | Sun, HY | ||||||
| dc.contributor.author | Li, GR | ||||||
| dc.date.accessioned | 2012-02-03T06:13:43Z | ||||||
| dc.date.available | 2012-02-03T06:13:43Z | ||||||
| dc.date.issued | 2012 | ||||||
| dc.description.abstract | Background 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.nature | Link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | British 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.doi | http://dx.doi.org/10.1111/j.1476-5381.2012.01831.x | ||||||
| dc.identifier.epage | 1150 | ||||||
| dc.identifier.hkuros | 198541 | ||||||
| dc.identifier.isi | WOS:000303923000026
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.issn | 0007-1188 2011 Impact Factor: 4.409 2011 SCImago Journal Rankings: 0.406 | ||||||
| dc.identifier.issue | 3 | ||||||
| dc.identifier.pmid | 22224416 | ||||||
| dc.identifier.scopus | eid_2-s2.0-84860843028 | ||||||
| dc.identifier.spage | 1140 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/144560 | ||||||
| dc.identifier.volume | 166 | ||||||
| dc.language | eng | ||||||
| dc.publisher | John 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.place | United Kingdom | ||||||
| dc.relation.ispartof | British Journal of Pharmacology | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.rights | British Journal of Pharmacology. Copyright © John Wiley & Sons Ltd. | ||||||
| dc.subject | ATP | ||||||
| dc.subject | cardiac fibroblasts | ||||||
| dc.subject | cell cycling | ||||||
| dc.subject | cell migration | ||||||
| dc.subject | proliferation | ||||||
| dc.title | Adenosine-5'-triphosphate up-regulates proliferation of human cardiac fibroblasts | ||||||
| dc.type | Article |
Author Affiliations
- Shenzhen University
- The University of Hong Kong Li Ka Shing Faculty of Medicine