RESUMO
Hepatocyte growth factor (HGF) has been shown to induce angiogenesis in vivo and has potential as a candidate gene for 'therapeutic angiogenesis'. In vivo, two isoforms of HGF, HGF723 and HGF728, consisting of 723 and 728 amino acids, are generated through alternative splicing between exons 4 and 5, but the biological effects of their coexpression have not yet been elucidated. In this study, we generated a series of genomic-complementary DNA (cDNA) hybrids of the HGF gene by inserting various truncated intron 4 into the junction of exons 4 and 5 of HGF cDNA and analyzed the biological activities of these hybrid constructs. We showed that: (1) the hybrid called HGF-X7, which contained 1502 base pairs of intron 4, could drive a higher level of HGF expression than other hybrid constructs and cDNAs of each isoform alone; (2) the pCK vector was most efficient for the gene expression of HGF-X7; (3) coexpression of both isoforms of HGF could more efficiently induce the migration of human umbilical vein endothelial cell (HUVEC) and of the mouse myoblast cell line C2C12 myoblasts than a single isoform of HGF and human vascular endothelial growth factor (VEGF)165 at a given concentration; (4) intramuscular administration of pCK-HGF-X7 resulted in transient and localized HGF expression in the injected muscle without an increase in the HGF protein levels in other tissues including serum; and (5) intramuscular injection of pCK-HGF-X7 could more efficiently increase the number of angiographically recognizable collateral vessels, as well as improve an intra-arterial Doppler wire-measured blood flow in the rabbit model of hindlimb ischemia when compared with the identical vector encoding VEGF165 gene. These results showed that transfer of the genomic-cDNA hybrid of the HGF gene could be used as a potential therapeutic approach to human vascular diseases.
Assuntos
Artérias , Circulação Colateral/efeitos dos fármacos , DNA/uso terapêutico , Terapia Genética , Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/metabolismo , Isquemia/terapia , Animais , Artérias/crescimento & desenvolvimento , Artérias/metabolismo , Linhagem Celular , Movimento Celular/efeitos dos fármacos , DNA/genética , DNA Complementar/genética , Modelos Animais de Doenças , Extremidades/irrigação sanguínea , Feminino , Expressão Gênica , Técnicas de Transferência de Genes , Engenharia Genética , Vetores Genéticos/genética , Fator de Crescimento de Hepatócito/farmacologia , Humanos , Íntrons/genética , Isquemia/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Coelhos , Fluxo Sanguíneo Regional/efeitos dos fármacosRESUMO
A new intra-system optical interconnection module directly integrated on a polymeric optical waveguide is suggested. A polymeric optical waveguide plays a role in the propagation path of optical signals from the transmitter to the receiver and in a platform integrated with various optical/electrical devices such as a vertical cavity surface emitting laser, photodiode, very large scale integrated circuit chips, and electrical connectors. Because the polymeric optical waveguide is simultaneously used as an integrated platform, the fabrication process of the optical interconnection module is very simple, and the proposed process is compatible with the conventional printed circuit board process. The suggested optical interconnection was also successfully demonstrated with a 5-Gb/s data transmission through the module directly integrated on a polymeric optical waveguide.
RESUMO
A new optical interconnection scheme based on a rigid flexible optical electrical printed circuit board (RFOE-PCB) is suggested. The easily installed RFOE-PCB can be universally applied for both chip- and board-level optical interconnections. This letter describes the detailed fabrication process, optical properties, and heat-resisting property of the RFOE-PCB. The fabricated RFOE-PCB was also successfully demonstrated with a 2.5-Gb/s data transmission through a 45 degrees-ended optical waveguide embedded in the RFOE-PCB.