Identification of Novel Trophoblast Invasion-Related Genes: Heme Oxygenase-1 Controls Motility via Peroxisome Proliferator-Activated Receptor γ

摘要: Invasion of cytotrophoblasts (CTBs) into uterine tissues is essential for placental development. To identify molecules regulating trophoblast invasion, mRNA signatures purified villous (CTB, poor invasiveness) and extravillous trophoblasts (EVTs) (high isolated from first trimester human placentae explant cultures, respectively, were compared using GeneChip analyses yielding 991 invasion/migration-related transcripts. Several genes involved in physiological pathological cell including A disintegrin metalloprotease-12, -19, -28, as well Spondin-2, up-regulated EVTs. Pathway prediction identified several functional modules associated with either the invasive or noninvasive phenotype. One that was down-regulated pool, heme oxygenase-1 (HO-1), selected analyses. Real-time PCR analyses, Western blotting, immunofluorescence differentiating cultures demonstrated down-regulation HO-1 EVTs CTBs. Modulation expression loss-of gain-of function models (BeWo HTR8/SVneo, respectively) an inverse relationship migration transwell wound healing assays. Importantly, led to increase protein levels activity nuclear hormone receptor peroxisome proliferator activated (PPAR) gamma. Pharmacological inhibition PPARgamma abrogated inhibitory effects on migration. Collectively, our results demonstrate gene profiling CTBs can be used unravel novel regulators invasion. Accordingly, we a negative regulator motility acting via up-regulation PPARgamma.