title: Possible participation of pICln in the regulation of angiogenesis through alternative splicing of vascular endothelial growth factor receptor mRNAs.
abstract: In this study, the authors applied a modified Antisense Display method to human vascular endothelial cells (ECs) in culture to isolate new angiostatic genes. Screening of a 10mer antisense oligodeoxyribonucleotide (oligo) repertoire identified a subpool that consistently stimulated EC growth. Subsequent screening of oligos with increasing chain length led to the isolation of a unique growth-stimulatory 14mer, 5'-TTCCACATCATATT-3'. cDNA/EST data-base search and expression analyses in ECs indicated pICln as the corresponding gene. A longer unique antisense oligo against a different region of pICln mRNA was found to also enhance EC growth and tube formation and to decrease mRNAs for soluble Flt-1 and neuropilin-1 vascular endothelial growth factor (VEGF) receptors, the angiostatic factors that are generated by alternative RNA splicing. Conversely,pICln overexpression suppressed EC growth and increased the mRNAs for both soluble Flt-1 and soluble neuropilin-1. The present findings thus suggest that pICln plays a role in autocrine regulation of angiogenesis, probably through alternative splicing.
authors.affiliation: Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, Takara-machi, Kanazawa, Japan.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Hideto
authors.initials: H
authors.lastname: Yonekura
authors.forename: Chul-Hee
authors.initials: CH
authors.lastname: Kim
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sakurai
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takiya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Futo
authors.forename: Takuo
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
mesh_terms: D017398:Alternative Splicing; D016375:Antisense Elements (Genetics); D006801:Humans; D018919:Neovascularization, Physiologic / Q000502:physiology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D016375:Antisense Elements (Genetics); D020033:Protein Isoforms; D012333:RNA, Messenger; D040262:Receptors, Vascular Endothelial Growth Factor