Inhibition of GSK3 Represses the Expression of Retinoic Acid Synthetic Enzyme ALDH1A2 via Wnt/β-Catenin Signaling in WiT49 Cells.

摘要: Organogenesis, including renal development, requires an appropriate retinoic acid concentration, which is established by differential expression of aldehyde dehydrogenase 1 family member A2 (ALDH1A2) and cytochrome P450 26 subfamily A/B/C (CYP26A1/B1/C1). In the fetal kidney, ALDH1A2 expresses in developing stroma vesicle its derivatives but does not present ureteric bud. It remains unclear what may contribute to this pattern. Here we show that glycogen synthase kinase 3 alpha/beta (GSK3A/B) inhibitor CHIR99021 significantly represses WiT49, a Wilms' tumor cell line exhibits "triphasic" potential used as kidney model. fails suppress β-catenin inhibited, suggesting downregulation through Wnt/β-catenin signaling. Ectopic mouse Wnt1, Wnt3a, Wnt4, Wnt9b WiT49 cells. Using immunohistochemistry, inverse correlation Aldh1a2 with rat E18.5 kidney. ChIP demonstrated recruited promoter, conserved intron1G, another site within intron ALDH1A2. luciferase assay, further promoter intron1G element are involved repression CHIR99021. Our work demonstrates can be directly repressed signaling cells, play role maintaining pattern thus controlling availability localization regulating aspects development.