title: Functional TRPV2 and TRPV4 channels in human cardiac c-kit(+) progenitor cells.
abstract: The cellular physiology and biology of human cardiac c-kit(+) progenitor cells has not been extensively characterized and remains an area of active research. This study investigates the functional expression of transient receptor potential vanilloid (TRPV) and possible roles for this ion channel in regulating proliferation and migration of human cardiac c-kit(+) progenitor cells. We found that genes coding for TRPV2 and TRPV4 channels and their proteins are significantly expressed in human c-kit(+) cardiac stem cells. Probenecid, an activator of TRPV2, induced an increase in intracellular Ca(2+) (Ca(2+) i ), an effect that may be attenuated or abolished by the TRPV2 blocker ruthenium red. The TRPV4 channel activator 4α-phorbol 12-13-dicaprinate induced Ca(2+) i oscillations, which can be inhibited by the TRPV4 blocker RN-1734. The alteration of Ca(2+) i by probenecid or 4α-phorbol 12-13-dicprinate was dramatically inhibited in cells infected with TRPV2 short hairpin RNA (shRNA) or TRPV4 shRNA. Silencing TRPV2, but not TRPV4, significantly reduced cell proliferation by arresting cells at the G0/G1 boundary of the cell cycle. Cell migration was reduced by silencing TRPV2 or TRPV4. Western blot revealed that silencing TRPV2 decreased expression of cyclin D1, cyclin E, pERK1/2 and pAkt, whereas silencing TRPV4 only reduced pAkt expression. Our results demonstrate for the first time that functional TRPV2 and TRPV4 channels are abundantly expressed in human cardiac c-kit(+) progenitor cells. TRPV2 channels, but not TRPV4 channels, participate in regulating cell cycle progression; moreover, both TRPV2 and TRPV4 are involved in migration of human cardiac c-kit(+) progenitor cells.
authors: Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
authors: Hui
authors: H
authors: Che
authors: Xiamen Cardiovascular Hospital, Medical College of Xiamen University, Xiamen, Fujian, China.
authors: Guo-Sheng
authors: GS
authors: Xiao
authors: Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
authors: Hai-Ying
authors: HY
authors: Sun
authors: Xiamen Cardiovascular Hospital, Medical College of Xiamen University, Xiamen, Fujian, China.
authors: Yan
authors: Y
authors: Wang
authors: Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.|Xiamen Cardiovascular Hospital, Medical College of Xiamen University, Xiamen, Fujian, China.
authors: Gui-Rong
authors: GR
authors: Li
mesh_terms: D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002465:Cell Movement; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D009206:Myocardium / Q000166:cytology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D050916:TRPV Cation Channels; C400769:TRPV2 protein, human; C416986:TRPV4 protein, human; D019009:Proto-Oncogene Proteins c-kit; D002118:Calcium
keywords: human cardiac c-kit+ progenitor cells; migration; proliferation; shRNA; transient receptor potential vanilloid channels