RESUMO
The changes in gene expression during senescence are very interesting. Early population doubling cDNA-1 (EPC-1, also known as pigment epithelial derived factor, PEDF) is one of the genes whose expression decreases dramatically during cellular aging. We examined whether or not EPC-1/PEDF promoter activity was affected by the cellular ageing using human diploid lung fibroblast cells in culture. Here we showed the promoter/enhancer region of EPC-1/PEDF existed at more than 1760 bp upstream from the transcriptional initiation site of the gene, and was regulated by both aging and cell cycle. These findings suggest that the expression of the EPC-1/PEDF gene is, at least in part, regulated transcriptionally in the cells. The analysis of the promoter region of the EPC-1/PEDF gene in this paper suggests the age- and cell cycle-dependent expression of specific transcriptional factor(s).
Assuntos
Ciclo Celular/genética , Senescência Celular/genética , Proteínas do Olho/genética , Fibroblastos/metabolismo , Fatores de Crescimento Neural/genética , Regiões Promotoras Genéticas , Serpinas/genética , Ciclo Celular/fisiologia , Células Cultivadas , Diploide , Proteínas do Olho/metabolismo , Humanos , Fatores de Crescimento Neural/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Serpinas/metabolismo , Sítio de Iniciação de Transcrição , Transcrição GênicaRESUMO
Aims: Patients with primary biliary cirrhosis (PBC) occasionally suffer complications from other autoimmune diseases. When PBC was associated with calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly and telangiectasias (CREST) symptoms, it has been proposed that it is a distinct clinical entity. This study aimed to investigate whether PBC associated with CREST symptoms is a distinct disease complex. Method: Clinicolaboratory data, HLA type of leukocytes and disease prognosis were compared between 31 patients with PBC associated with CREST symptoms and 68 patients with PBC alone. Results: The characteristic findings and significant differences observed in patients with PBC associated with CREST symptoms compared with PBC alone are as follows: all women with older age with milder clinical features of both PBC (asymptomatic PBC in 84%) and CREST syndrome (incomplete CREST in 81%), more frequent occurrence of esophageal varices (28.6 vs. 9.3%), better prognosis (87.5 vs. 45.5% in 10 years survival), lower serum levels of AST (39.8 vs. 63.6 IU/l) and IgM (460 vs. 676 mg/dl), higher prevalence of discrete speckled pattern of antinuclear antibodies (93.5 vs. 12.3%), higher median titers of anti-CENP-B antibodies (1.22 vs. 0.31), lower median titers of antimitochondrial antibody (1:80 vs. 1:160), and a higher prevalence of HLA-DR9 (54.5 vs. 24.3%). Conclusion: These findings support the presence of a subgroup in PBC as PBC associated with CREST symptoms.
