File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Angiotensin II upregulates KCa3.1 channels and stimulates cell proliferation in rat cardiac fibroblasts

TitleAngiotensin II upregulates KCa3.1 channels and stimulates cell proliferation in rat cardiac fibroblasts
Authors
KeywordsAngiotensin II
Cardiac fibroblasts
Intermediate-conductance Ca2+ activated K+ channels
Proliferation
Issue Date2013
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/biochempharm
Citation
Biochemical Pharmacology, 2013, v. 85 n. 10, p. 1486-1494 How to Cite?
AbstractThe proliferation of cardiac fibroblasts is implicated in the pathogenesis of myocardial remodeling and fibrosis. Intermediate-conductance calcium-activated K+ channels (KCa3.1 channels) have important roles in cell proliferation. However, it is unknown whether angiotensin II (Ang II), a potent profibrotic molecule, would regulate KCa3.1 channels in cardiac fibroblasts and participate in cell proliferation. In the present study, we investigated whether KCa3.1 channels were regulated by Ang II, and how the channel activity mediated cell proliferation in cultured adult rat cardiac fibroblasts using electrophysiology and biochemical approaches. It was found that mRNA, protein, and current density of KCa3.1 channels were greatly enhanced in cultured cardiac fibroblasts treated with 1 μM Ang II, and the effects were countered by the angiotensin type 1 receptor (AT1R) blocker losartan, the p38-MAPK inhibitor SB203580, the ERK1/2 inhibitor PD98059, and the PI3K/Akt inhibitor LY294002. Ang II stimulated cell proliferation and the effect was antagonized by the KCa3.1 blocker TRAM-34 and siRNA targeting KCa3.1. In addition, Ang II-induced increase of KCa3.1 expression was attenuated by transfection of activator protein-1 (AP-1) decoy oligodeoxynucleotides. These results demonstrate for the first time that Ang II stimulates cell proliferation mediated by upregulating KCa3.1 channels via interacting with the AT1R and activating AP-1 complex through ERK1/2, p38-MAPK and PI3K/Akt signaling pathways in cultured adult rat cardiac fibroblasts.
Persistent Identifierhttp://hdl.handle.net/10722/183748
ISSN
2017 Impact Factor: 4.235
2015 SCImago Journal Rankings: 2.263
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, LP-
dc.contributor.authorWang, Y-
dc.contributor.authorZhao, LM-
dc.contributor.authorLi, GR-
dc.contributor.authorDeng, XL-
dc.date.accessioned2013-06-18T04:12:42Z-
dc.date.available2013-06-18T04:12:42Z-
dc.date.issued2013-
dc.identifier.citationBiochemical Pharmacology, 2013, v. 85 n. 10, p. 1486-1494-
dc.identifier.issn0006-2952-
dc.identifier.urihttp://hdl.handle.net/10722/183748-
dc.description.abstractThe proliferation of cardiac fibroblasts is implicated in the pathogenesis of myocardial remodeling and fibrosis. Intermediate-conductance calcium-activated K+ channels (KCa3.1 channels) have important roles in cell proliferation. However, it is unknown whether angiotensin II (Ang II), a potent profibrotic molecule, would regulate KCa3.1 channels in cardiac fibroblasts and participate in cell proliferation. In the present study, we investigated whether KCa3.1 channels were regulated by Ang II, and how the channel activity mediated cell proliferation in cultured adult rat cardiac fibroblasts using electrophysiology and biochemical approaches. It was found that mRNA, protein, and current density of KCa3.1 channels were greatly enhanced in cultured cardiac fibroblasts treated with 1 μM Ang II, and the effects were countered by the angiotensin type 1 receptor (AT1R) blocker losartan, the p38-MAPK inhibitor SB203580, the ERK1/2 inhibitor PD98059, and the PI3K/Akt inhibitor LY294002. Ang II stimulated cell proliferation and the effect was antagonized by the KCa3.1 blocker TRAM-34 and siRNA targeting KCa3.1. In addition, Ang II-induced increase of KCa3.1 expression was attenuated by transfection of activator protein-1 (AP-1) decoy oligodeoxynucleotides. These results demonstrate for the first time that Ang II stimulates cell proliferation mediated by upregulating KCa3.1 channels via interacting with the AT1R and activating AP-1 complex through ERK1/2, p38-MAPK and PI3K/Akt signaling pathways in cultured adult rat cardiac fibroblasts.-
dc.languageeng-
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/biochempharm-
dc.relation.ispartofBiochemical Pharmacology-
dc.subjectAngiotensin II-
dc.subjectCardiac fibroblasts-
dc.subjectIntermediate-conductance Ca2+ activated K+ channels-
dc.subjectProliferation-
dc.titleAngiotensin II upregulates KCa3.1 channels and stimulates cell proliferation in rat cardiac fibroblasts-
dc.typeArticle-
dc.identifier.emailWang, Y: hannayan@hku.hk-
dc.identifier.emailLi, GR: grli@hkucc.hku.hk-
dc.identifier.authorityLi, GR=rp00476-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.bcp.2013.02.032-
dc.identifier.pmid23500546-
dc.identifier.scopuseid_2-s2.0-84876677892-
dc.identifier.hkuros214564-
dc.identifier.volume85-
dc.identifier.issue10-
dc.identifier.spage1486-
dc.identifier.epage1494-
dc.identifier.isiWOS:000319371800009-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats