RESUMO
During pregnancy, placental growth allows the adaptation of the feto-maternal unit to fetal requirements. Placental alkaline phosphatase (PLAP) is a phosphomonoesterase produced increasingly until term by the placenta and also ectopically in some tumors. To precise the role of this enzyme in the placenta, we analyzed the genome wide expression profile of HTR-8/Svneo trophoblastic cells after overexpression of the alkaline phosphatase gene (ALPP). We showed that ALPP overexpression mainly altered expression of genes implicated in cellular growth and proliferation. These results were confirmed by the study of cellular effects in HTR-8/Svneo cells overexpressing ALPP and in HTR-8/Svneo cells in which ALPP expression was suppressed by siRNA. We showed that PLAP exerts a positive effect on DNA replication and acts as a proliferative factor in trophoblastic cells.
Assuntos
Fosfatase Alcalina/biossíntese , Isoenzimas/biossíntese , Placenta/fisiologia , Trofoblastos/fisiologia , Fosfatase Alcalina/genética , Processos de Crescimento Celular/genética , Linhagem Celular , Feminino , Proteínas Ligadas por GPI/biossíntese , Proteínas Ligadas por GPI/genética , Perfilação da Expressão Gênica , Humanos , Isoenzimas/genética , Modelos Lineares , Análise de Sequência com Séries de Oligonucleotídeos , Placenta/citologia , Placenta/enzimologia , Placenta/metabolismo , Gravidez , RNA/química , RNA/genética , RNA Interferente Pequeno/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Trofoblastos/citologia , Trofoblastos/enzimologia , Trofoblastos/metabolismoRESUMO
Placental alkaline phosphatase (PLAP), encoded by the ALPP gene, is produced by the fetal side of the placenta. This enzyme displays strong genetic variability. Some of the variants were reported to be associated with pathology of pregnancy. We show here that the two most common ALPP allelic variants, Pl(1) and Pl(2), differ in mRNA expression level. This differential expression was independent of the parental origin and probably results from linkage disequilibrium with the sequence variation rs2014683G>A in the ALPP gene promoter that was shown to have allele-specific binding patterns to placental nuclear proteins. The possible role of this allelic-specific expression in placenta-related pathology is discussed.
