RESUMO
The early growth response gene-1 (Egr-1), a zinc finger transcriptional regulator, was induced in a rat model of mesangioproliferative glomerulonephritis (GN). Northern blot analysis revealed a maximal 14.9-fold increase in glomerular Egr-1 mRNA at day 6 of GN. By immunohistochemistry Egr-1 protein expression was demonstrated to be mainly confined to glomerular mesangial cells (MC). To test whether Egr-1 directly regulates MC proliferation, cultured MCs were stimulated with platelet-derived growth factor (PDGF) after preincubation with different Egr-1 antisense oligonucleotides (ASOs). PDGF-induced rise in 3H-thymidine uptake by 83% and almost completely abrogated increase in MC number. We conclude that Egr-1 induction is of critical importance for PDGF-induced mitogenic signaling in MCs, and inhibition of Egr-1 in vivo may offer an approach to oppose glomerular MC proliferation in glomerular inflammatory disease.
Assuntos
Proteínas de Ligação a DNA/genética , Mesângio Glomerular/metabolismo , Mesângio Glomerular/patologia , Glomerulonefrite Membranoproliferativa/genética , Glomerulonefrite Membranoproliferativa/patologia , Proteínas Imediatamente Precoces , Fatores de Transcrição/genética , Animais , Sequência de Bases , Divisão Celular , Células Cultivadas , Proteínas de Ligação a DNA/metabolismo , Proteína 1 de Resposta de Crescimento Precoce , Expressão Gênica/efeitos dos fármacos , Mesângio Glomerular/efeitos dos fármacos , Glomerulonefrite Membranoproliferativa/metabolismo , Masculino , Oligonucleotídeos Antissenso/genética , Oligonucleotídeos Antissenso/farmacologia , Fator de Crescimento Derivado de Plaquetas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Timidina/metabolismo , Fatores de Transcrição/metabolismo , Dedos de Zinco/genéticaRESUMO
The authors report on an international collaboration that uses the Internet for medical education. In addition to introducing the students to electronic communication, the project aims to further international collaboration and understanding and to emphasize the importance of a population perspective for health and disease. Students and professors in Canada, England and Hungary participated.
