Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Universidad Nacional de Córdoba, Argentina.
Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, Argentina.
FEBS Lett. 2022 Jul;596(13):1700-1719. doi: 10.1002/1873-3468.14367. Epub 2022 May 11.
Trophoblast cell differentiation is of paramount importance for successful pregnancy. Krüppel-like factor 6 (KLF6), a transcription factor with diverse roles in cell physiology and tumor biology, is required for trophoblast differentiation through the syncytial pathway. Herein, we demonstrate that extravillous trophoblast (EVT) cell migration and mesenchymal phenotype are increased upon KLF6 downregulation or the expression of a deletion mutant lacking its transcriptional regulatory domain (KΔac). Raman spectroscopy revealed molecular modifications compatible with increased differentiation in cells stably expressing the KΔac mutant. Moreover, abnormally invasive placenta showed lower KLF6 immunostaining compared with the normal placenta. Thus, impaired KLF6 expression or function stimulates EVT migration and differentiation in vitro and may contribute to the physiopathology of the abnormally invasive placenta.
滋养细胞分化对于成功妊娠至关重要。Krüppel 样因子 6（KLF6）是一种转录因子，在细胞生理学和肿瘤生物学中具有多种作用，通过合胞体途径促进滋养细胞分化。在此，我们证明下调 KLF6 或表达缺乏转录调节域的缺失突变体（KΔac）可增加绒毛外滋养细胞（EVT）的迁移和间充质表型。拉曼光谱显示，稳定表达 KΔac 突变体的细胞中存在与分化增加相兼容的分子修饰。此外，异常侵袭性胎盘的 KLF6 免疫染色比正常胎盘低。因此，KLF6 表达或功能受损可刺激 EVT 在体外迁移和分化，并可能导致异常侵袭性胎盘的病理生理学改变。
