RESUMEN
The co-stimulatory molecule CD28 plays an important role in T-cell-mediated immune response like acute cellular liver transplant rejection. The aim of the retrospective case- control study was to examine whether the single nucleotide polymorphisms (SNPs) rs3116487, rs3116494, and rs3116496 of the CD28 gene are associated with acute cellular liver transplant rejection. The mentioned SNPs were genotyped in 147 liver transplant recipients without acute cellular rejection and 144 liver transplant recipients with acute cellular rejection by real-time endpoint genotyping. The genotype and allele frequencies of the SNPs did not show any significant differences between both groups. Haplotype analyzes of the SNPs also showed no association. Our data suggest that the analyzed SNPs are not major contributors to the susceptibility of acute cellular liver transplant rejection.
Asunto(s)
Antígenos CD28/genética , Rechazo de Injerto/genética , Supervivencia de Injerto/genética , Trasplante de Hígado/efectos adversos , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Alelos , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Rechazo de Injerto/inmunología , Supervivencia de Injerto/inmunología , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
The PTPN22 gene encodes the lymphoid protein tyrosine phosphatase involved in regulation the immune response. The single nucleotide polymorphisms (SNPs) rs1217388, rs1310182, rs2476601, and rs2488457 are located within the PTPN22 gene. We investigated whether these SNPs in liver transplant donors are associated with acute cellular rejection in the recipients. The SNPs were analyzed in donors (n = 104) of recipients who did not develop an acute cellular rejection and in donors (n = 53) of corresponding recipients developing an acute cellular rejection. No significant differences in genotype and allele frequencies of these SNPs were detected in either of the group. Our data suggest that these SNPs in liver transplant donors have no impact on the susceptibility of acute cellular liver transplant rejection.
Asunto(s)
Rechazo de Injerto , Trasplante de Hígado , Proteína Tirosina Fosfatasa no Receptora Tipo 22 , Alelos , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Rechazo de Injerto/genética , Humanos , Polimorfismo de Nucleótido Simple , Proteína Tirosina Fosfatasa no Receptora Tipo 22/genética , Donantes de TejidosRESUMEN
The single nucleotide polymorphisms (SNPs) rs4794067, rs2275806, rs2232365, and rs3761548 map in the genes of TBX21, GATA3, and FOXP3 involved in mediating acute cellular rejection. We investigated whether these SNPs are associated with acute cellular liver transplant rejection. The SNPs were analyzed in recipients with early acute cellular rejection (n = 97), recipients with late acute cellular rejection (n = 49), and recipients without rejection (n = 149). There was no association between acute cellular rejection and SNPs rs4794067, rs2275806, and rs2232365. In contrast, the allele -3279A of FOXP3 SNP rs3761548 exhibited a higher frequency in recipients with late acute cellular rejection as compared with recipients without rejection. This result indicates that the allele -3279A of the SNP rs3761548 may predispose to the development of late acute cellular rejection.
Asunto(s)
Factores de Transcripción Forkhead/genética , Factor de Transcripción GATA3/genética , Rechazo de Injerto/etiología , Rechazo de Injerto/genética , Trasplante de Hígado/efectos adversos , Polimorfismo de Nucleótido Simple/genética , Proteínas de Dominio T Box/genética , Biopsia , Femenino , Rechazo de Injerto/patología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The cytoskeleton plays a central role for the integration of biochemical and biomechanical signals across the cell required for complex cellular functions. Recent studies indicate that the intermediate filament vimentin is necessary for endothelial cell morphogenesis e.g. in the context of leukocyte transmigration. Here, we present evidence, that the scaffold provided by vimentin is essential for VASP localization and PKG mediated VASP phosphorylation and thus controls endothelial cell migration and proliferation. Vimentin suppression using siRNA technique significantly decreased migration velocity by 50% (videomicroscopy), diminished transmigration activity by 42.5% (Boyden chamber) and reduced proliferation by 43% (BrdU-incorporation). In confocal microscopy Vimentin colocalized with VASP and PKG in endothelial cells. Vimentin suppression was accompanied with a translocation of VASP from focal contacts to the perinuclear region. VASP/Vimentin and PKG/Vimentin colocalization appeared to be essential for proper PKG mediated VASP phosphorylation because we detected a diminished expression of PKG and p(Ser239)-VASP in vimentin-suppressed cells, Furthermore, the induction of VASP phosphorylation in perfused arteries was markedly decreased in vimentin knockout mice compared to wildtypes. A link is proposed between vimentin, VASP phosphorylation and actin dynamics that delivers an explanation for the important role of vimentin in controlling endothelial cell morphogenesis.