Possible participation of pICln in the regulation of angiogenesis through alternative splicing of vascular endothelial growth factor receptor mRNAs.
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.
Li
Hui
H
Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, Takara-machi, Kanazawa, Japan.
Yonekura
Hideto
H
Kim
Chul-Hee
CH
Sakurai
Shigeru
S
Yamamoto
Yasuhiko
Y
Takiya
Toshiyuki
T
Futo
Satoshi
S
Watanabe
Takuo
T
Yamamoto
Hiroshi
H
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*
D016375:Antisense Elements (Genetics); D020033:Protein Isoforms; D012333:RNA, Messenger; D040262:Receptors, Vascular Endothelial Growth Factor