title: Knockdown of transient receptor potential canonical-1 reduces the proliferation and migration of endothelial progenitor cells.
abstract: Endothelial progenitor cells (EPCs) play an important role in accelerating endothelial repair after vascular injury. The proliferation and migration of EPCs is a critical first step in restoring endothelial. However, mechanisms for modulating EPC proliferation and migration are still being elucidated. Our previous study found that transient receptor potential canonical-1 (TRPC1) is involved in regulating store-operated Ca(2+) entry in EPCs through stromal interaction molecule 1. Therefore, in the present study, we sought to further investigate the regulation of proliferation and migration of EPCs by TRPC1. We found that the silencing of TRPC1 by 2 different RNA interference methods suppressed the proliferation and migration of EPCs. In addition, knockdown of TRPC1 significantly reduced of the amplitude of store-operated Ca(2+) entry and caused arrest of the EPC cell cycle in G1 phase. Analysis of the expression of 84 cell cycle genes by microarray showed that 9 genes were upregulated and 4 were downregulated by >2-fold in EPCs following TRPC1 silencing. The genes with expression changes were Ak1, Brca2, Camk2b, p21, Ddit3, Inha, Slfn1, Mdm2, Prm1, Bcl2, Mki67, Pmp22, and Ppp2r3a. Finally, we found that a Schlafen 1-blocking peptide partially reversed the abnormal cell cycle distribution and proliferation induced by TRPC1 knockdown, suggesting that Schlafen 1 is downstream of TRPC1 silencing in regulating EPC proliferation. In summary, these findings provide a new mechanism for modulating the biological properties of EPCs and suggest that TRPC1 may be a new target for inducing vascular repair by EPCs.
authors.affiliation: Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Chun-yan
authors.initials: CY
authors.lastname: Kuang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Kui
authors.initials: K
authors.lastname: Wang
authors.forename: De-hui
authors.initials: DH
authors.lastname: Qian
authors.forename: Meng-yang
authors.initials: MY
authors.lastname: Den
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D059585:G1 Phase Cell Cycle Checkpoints; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D051381:Rats; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D015415:Biomarkers; D018797:Cell Cycle Proteins; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D002118:Calcium