Abstract
The oncogene B-cell lymphoma 6 (BCL6) is associated with lymphomagenesis. Intriguingly, its expression is increased in preeclamptic placentas. Preeclampsia is one of the leading causes of maternal and perinatal mortality and morbidity. Preeclamptic placentas are characterized by various defects like deregulated differentiation and impaired fusion of trophoblasts. Its pathogenesis is however not totally understood. We show here that BCL6 is present throughout the cell fusion process in the fusogenic trophoblastic cell line BeWo. Suppression of BCL6 promotes trophoblast fusion, indicated by enhanced levels of fusion-related β-hCG, syncytin 1 and syncytin 2. Increased mRNA levels of these genes could also be observed in primary term cytotrophoblasts depleted of BCL6. Conversely, stable overexpression of BCL6 reduces the fusion capacity of BeWo cells. These data suggest that an accurately regulated expression of BCL6 is important for proper differentiation and successful syncytialization of trophoblasts. While deregulated BCL6 is linked to lymphomagenesis by blocking lymphocyte terminal differentiation, increased BCL6 in the placenta contributes to the development of preeclampsia by impairing trophoblast differentiation and fusion.
Highlights
The oncogene B-cell lymphoma 6 (BCL6), a key regulator of B-lymphocyte development, is a transcriptional repressor and often deregulated in lymphomas [1]
While deregulated BCL6 is linked to lymphomagenesis by blocking lymphocyte terminal differentiation, increased BCL6 in the placenta contributes to the development of preeclampsia by impairing trophoblast differentiation and fusion
The gene expression of BCL6 was increasing during this fusion process after an initial reduction at 24 h, in a less extent, compared to BeWo cells treated with dimethyl sulfoxide (DMSO) (Figure 1C), indicating that differentiation is associated with less BCL6 gene expression
Summary
The oncogene B-cell lymphoma 6 (BCL6), a key regulator of B-lymphocyte development, is a transcriptional repressor and often deregulated in lymphomas [1]. Besides B-cell activation and differentiation, BCL6 is known to play roles in the DNA damage response, cell cycle regulation and apoptosis induction of lymphocytes [2, 3], as well as in invasion, migration and proliferation of breast cancer cells [4]. Preeclampsia (PE), the most common disease that complicates pregnancy, is one of the leading causes of maternal and perinatal mortality and morbidity worldwide [9, 10]. It is a consequence of diverse pathophysiological processes and characterized by the de novo onset of concurrent hypertension and proteinuria in the second half of gestation [11, 12]. PE is linked to profound cellular dysfunctions of trophoblasts including deregulated proliferation, impaired differentiation, defective fusion and increased syncytiotrophoblastic microparticles due to dysfunction of apoptosis resulting in reduced STB area [16]
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