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- Publisher Website: 10.1152/ajpcell.00268.2008
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Article: Regulation of cell proliferation by intermediate-conductance Ca 2+-activated potassium and volume-sensitive chloride channels in mouse mesenchymal stem cells
Title | Regulation of cell proliferation by intermediate-conductance Ca 2+-activated potassium and volume-sensitive chloride channels in mouse mesenchymal stem cells |
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Authors | |
Keywords | Cell cycle progression Intermediate conductance Ca2+-activated K+ current Short interference RNA Volume sensitive Cl- current |
Issue Date | 2008 |
Publisher | American Physiological Society. The Journal's web site is located at http://intl-ajpcell.physiology.org/ |
Citation | American Journal Of Physiology - Cell Physiology, 2008, v. 295 n. 5, p. C1409-C1416 How to Cite? |
Abstract | Bone marrow mesenchymal stem cells (MSCs) are a promising cell source for regenerative medicine; however, their cellular physiology is not fully understood. The present study aimed at exploring the potential roles of the two dominant functional ion channels, intermediate-conductance Ca 2+-activated potassium (IKCa) and volume-sensitive chloride (ICl.vol) channels, in regulating proliferation of mouse MSCs. We found that inhibition of IKCa with clotrimazole and I Cl.vol with 5-nitro-1-(3-phenylpropylamino) benzoic acid (NPPB) reduced cell proliferation in a concentration-dependent manner. Knockdown of KCa3.1 or Clcn3 with specific short interference (si)RNAs significantly reduced IKCa or ICl.vol density and channel protein and produced a remarkable suppression of cell proliferation (by 24.4 ± 9.6% and 29.5 ± 7.2%, respectively, P < 0.05 vs. controls). Flow cytometry analysis showed that mouse MSCs retained at G0/G1 phase (control: 51.65 ± 3.43%) by inhibiting IKCa or ICl.vol using clotrimazole (2 μM: 64.45 ± 2.20%, P < 0.05) or NPPB (200 μM: 82.89 ± 2.49%, P < 0.05) or the specific siRNAs, meanwhile distribution of cells in S phase was decreased. Western blot analysis revealed a reduced expression of the cell cycle regulatory proteins cyclin D1 and cyclin E. Collectively, our results have demonstrated that IKCa and I Cl.vol channels regulate cell cycle progression and proliferation of mouse MSCs by modulating cyclin D1 and cyclin E expression. Copyright © 2008 the American Physiological Society. |
Persistent Identifier | http://hdl.handle.net/10722/163217 |
ISSN | 2023 Impact Factor: 5.0 2023 SCImago Journal Rankings: 1.711 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Tao, R | en_US |
dc.contributor.author | Lau, CP | en_US |
dc.contributor.author | Tse, HF | en_US |
dc.contributor.author | Li, GR | en_US |
dc.date.accessioned | 2012-09-05T05:28:49Z | - |
dc.date.available | 2012-09-05T05:28:49Z | - |
dc.date.issued | 2008 | en_US |
dc.identifier.citation | American Journal Of Physiology - Cell Physiology, 2008, v. 295 n. 5, p. C1409-C1416 | en_US |
dc.identifier.issn | 0363-6143 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/163217 | - |
dc.description.abstract | Bone marrow mesenchymal stem cells (MSCs) are a promising cell source for regenerative medicine; however, their cellular physiology is not fully understood. The present study aimed at exploring the potential roles of the two dominant functional ion channels, intermediate-conductance Ca 2+-activated potassium (IKCa) and volume-sensitive chloride (ICl.vol) channels, in regulating proliferation of mouse MSCs. We found that inhibition of IKCa with clotrimazole and I Cl.vol with 5-nitro-1-(3-phenylpropylamino) benzoic acid (NPPB) reduced cell proliferation in a concentration-dependent manner. Knockdown of KCa3.1 or Clcn3 with specific short interference (si)RNAs significantly reduced IKCa or ICl.vol density and channel protein and produced a remarkable suppression of cell proliferation (by 24.4 ± 9.6% and 29.5 ± 7.2%, respectively, P < 0.05 vs. controls). Flow cytometry analysis showed that mouse MSCs retained at G0/G1 phase (control: 51.65 ± 3.43%) by inhibiting IKCa or ICl.vol using clotrimazole (2 μM: 64.45 ± 2.20%, P < 0.05) or NPPB (200 μM: 82.89 ± 2.49%, P < 0.05) or the specific siRNAs, meanwhile distribution of cells in S phase was decreased. Western blot analysis revealed a reduced expression of the cell cycle regulatory proteins cyclin D1 and cyclin E. Collectively, our results have demonstrated that IKCa and I Cl.vol channels regulate cell cycle progression and proliferation of mouse MSCs by modulating cyclin D1 and cyclin E expression. Copyright © 2008 the American Physiological Society. | en_US |
dc.language | eng | en_US |
dc.publisher | American Physiological Society. The Journal's web site is located at http://intl-ajpcell.physiology.org/ | en_US |
dc.relation.ispartof | American Journal of Physiology - Cell Physiology | en_US |
dc.subject | Cell cycle progression | - |
dc.subject | Intermediate conductance Ca2+-activated K+ current | - |
dc.subject | Short interference RNA | - |
dc.subject | Volume sensitive Cl- current | - |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Cell Cycle - Drug Effects | en_US |
dc.subject.mesh | Cell Proliferation - Drug Effects | en_US |
dc.subject.mesh | Cell Size | en_US |
dc.subject.mesh | Cells, Cultured | en_US |
dc.subject.mesh | Chloride Channels - Antagonists & Inhibitors - Metabolism | en_US |
dc.subject.mesh | Clotrimazole - Pharmacology | en_US |
dc.subject.mesh | Cyclin D1 - Metabolism | en_US |
dc.subject.mesh | Cyclin E - Metabolism | en_US |
dc.subject.mesh | Dose-Response Relationship, Drug | en_US |
dc.subject.mesh | Intermediate-Conductance Calcium-Activated Potassium Channels - Antagonists & Inhibitors - Genetics - Metabolism | en_US |
dc.subject.mesh | Membrane Potentials | en_US |
dc.subject.mesh | Mesenchymal Stem Cells - Drug Effects - Metabolism | en_US |
dc.subject.mesh | Mice | en_US |
dc.subject.mesh | Mice, Inbred C57bl | en_US |
dc.subject.mesh | Nitrobenzoates - Pharmacology | en_US |
dc.subject.mesh | Potassium Channel Blockers - Pharmacology | en_US |
dc.subject.mesh | Rna Interference | en_US |
dc.subject.mesh | Rna, Small Interfering - Metabolism | en_US |
dc.title | Regulation of cell proliferation by intermediate-conductance Ca 2+-activated potassium and volume-sensitive chloride channels in mouse mesenchymal stem cells | en_US |
dc.type | Article | en_US |
dc.identifier.email | Tse, HF:hftse@hkucc.hku.hk | en_US |
dc.identifier.email | Li, GR:grli@hkucc.hku.hk | en_US |
dc.identifier.authority | Tse, HF=rp00428 | en_US |
dc.identifier.authority | Li, GR=rp00476 | en_US |
dc.description.nature | link_to_OA_fulltext | en_US |
dc.identifier.doi | 10.1152/ajpcell.00268.2008 | en_US |
dc.identifier.pmid | 18815226 | - |
dc.identifier.scopus | eid_2-s2.0-57349113856 | en_US |
dc.identifier.hkuros | 152676 | - |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-57349113856&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 295 | en_US |
dc.identifier.issue | 5 | en_US |
dc.identifier.spage | C1409 | en_US |
dc.identifier.epage | C1416 | en_US |
dc.identifier.isi | WOS:000262909800035 | - |
dc.publisher.place | United States | en_US |
dc.identifier.scopusauthorid | Tao, R=7102857104 | en_US |
dc.identifier.scopusauthorid | Lau, CP=7401968501 | en_US |
dc.identifier.scopusauthorid | Tse, HF=7006070805 | en_US |
dc.identifier.scopusauthorid | Li, GR=7408462932 | en_US |
dc.identifier.issnl | 0363-6143 | - |