Functional analysis of p21Cip1/CDKN1A in trophoblastic cells of the placenta and its roles in preeclampsia

• Applicant: Dr. Nina-Naomi Kreis
• Subject Area: Cell Biology
• Term: from 2017 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 390921723

Preeclampsia (PE), a serious disease during pregnancy, is the most common cause of maternal and perinatal mortality and morbidity contributing to long-term complications in mother and offspring. PE is associated with profound placental cellular dysfunctions characterized by altered proliferation, differentiation, fusion, invasion, apoptosis, autophagy and senescence. Interestingly, tumor progression and pregnancy share many common features. The cell cycle inhibitor p21Cip1/CDKN1A (p21), being tumor suppressor or oncogene depending on its localization, plays key roles in molecular oncology by regulating different cellular processes. Although placental development depends on the precise coordination of trophoblast proliferation and differentiation, little is known about cell cycle regulators like p21. In fact, it has been reported that the expression of p21 is important for placental development and altered in PE. It is therefore tempting to propose that p21 is crucial for the functionality of trophoblasts and its deregulation could contribute to its pathogenesis. To investigate this hypothesis, the expression, localization and molecular roles of p21 in various trophoblastic cell lines as well as primary placental tissues subdivided in different stages of PE will be systematically addressed. Despite intensive research, the pathogenesis of PE is not totally understood and no therapy is currently available. It is of clinical relevance to elucidate the complexity of PE and to gain further insight into its altered molecular pathways. General findings concerning p21s role in PE are pivotal for trophoblast biology and will contribute to the understanding of this severe unpredictable and unpreventable disease. In addition, trophoblasts offer an extremely attractive model for cancer and stem cell research.

• DFG Programme: Research Grants