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Understanding the relationship between autophagy and inflammasome activity in the human trophoblast

Grant number: 14/25802-5
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): May 01, 2015
Effective date (End): October 31, 2015
Field of knowledge:Health Sciences - Medicine - Maternal and Child Health
Principal Investigator:Maria Terezinha Serrão Peraçoli
Grantee:Ingrid Cristina Weel
Supervisor abroad: Vikki M. Abrahams
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Local de pesquisa : Yale School of Medicine (YSM), United States  
Associated to the scholarship:13/00535-1 - Evaluation of NLRP3 inflammasome and autophagy in placenta of pregnant women with preeclampsia, BP.DR

Abstract

Autophagy is an intracellular catabolic process which removes damaged organelles and cytoplasmatic proteins in order to maintain cellular homeostasis. However, autophagy is also involved in the regulation of immune function and inflammation. Two distinct maternal diseases, antiphospholipid syndrome (APS) and diabetes, are associated with placental inflammation and are clinical risk factors for preeclampsia development. Antiphospholipid syndrome (APS) is characterized by high titers of antiphospholipid antibodies (aPL), while diabetes in associated with high glucose levels. Studies have demonstrated that human first trimester trophoblast cells exposed to either aPL or high levels of glucose trigger the cells to secrete elevated levels of the pro-inflammatory cytokine IL-1² and this is mediated by the Nalp3 inflamasome. The central hypothesis of this project is that aPL/excess glucose induce an trophoblast pro-inflammatory response by inhibiting basal autophagy leading to inflammasome activation. To evaluate the crosstalk between autophagy and inflammasome on first trimester trophoblast induced with aPL or excess glucose, our specific aims are:1.To evaluate the effect of aPL or excess glucose on human first trimester extravillous trophoblast cell autophagy 2.To determine the role of the inflammasome on the trophoblast autophagic response to aPL or excess glucose. 3.To determine the role of autophagy on trophoblast inflammasome activation. The findings generated from this study may contribute to a better understanding of the mechanisms involved in trophoblast responses to aPL and excess glucose, mechanisms that could lead to preeclampsia, and the relationship between autophagy and the inflammasome in the placenta. (AU)