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Sdf2 factor in the activation of the Unfolded Protein Response (UPR) signaling network in the trophoblast physiology and pathology


Changes in placental function are known by the immediate consequences of pregnancy and fetus, and more recently by the possible influence on the long-term health of the newborn. In this context, there is an urgent need for studies that emphasize not only its structure but to define this organ biologically. Uniquely, the placenta plays a wide variety of functions, assuming activities of all major organ systems to allow the fetus to differentiate and mature.The maternal component of the human placenta is the endometrium, which early differentiates in the decidua. Formed by few layers, but with a wide variety of cell types, the decidua constitutes the basal plate of the placenta and is vitally important for the physiology of pregnancy. The fetal part of the placenta is also complex. The maternal blood spilled in intervillous spaces directly contacts the chorionic villi, a mesenchymal vascularized axis covered by a syncytial layer, the syncytiotrophoblast and cytotrophoblast cells (depending on the gestational stage). In this region, molecular exchanges occur between maternal and fetal organisms. At the contact of the chorionic villi with the decidua, cytotrophoblast cells grow and invade the maternal tissue assuming different morphologies and functions, featuring subtypes of extravillous cytotrophoblast cells, essentials for metabolic, immunological and functional, gestational homeostasis.Our laboratory has focused over the past 30 years to the study of trophoblast cells using, most recently as a model, the human placenta. We have been particularly interested in the expression of factors associated with the dialogue that develops at the maternal-fetal interface, working in placental homeostasis and consequently in pregnancy success. The main actor of these studies has been the trophoblast cells.In this project, we intend to analyze the participation of SDF2 protein in the endoplasmic reticulum stress in human trophoblast cells under normal conditions (using trophoblast cell lineages) and pathological conditions (human placental cells treated with serum from women with preeclampsia). Two important aspects should be highlighted about this study: i) Factors adverse to cell physiology can alter the homeostasis of the endoplasmic reticulum (ER), leading to a buildup of malformed proteins, which is known as ER Stress. This phenomenon activates specific responses (UPR Unfolded Protein Response), which can lead to the degradation of these proteins, increasing the survivability of the cell, even under stress; ii) Previous results from our laboratory have shown that when the gene SDF2 is silenced, the main regulatory factors of the UPR pathway associated with survival and / or cell death, were altered in trophoblast cells.Thus, based on the fact that the control of cell death and survival, crucial in maintaining any tissue / organ, is also a key factor in the formation of a healthy placenta or in the development of gestational diseases, we propose to investigate the roles played by SDF2 in ER stress pathway and its relations with the survival / apoptosis regulation in trophoblast cells under normal conditions and in the major pregnancy disorder, the preeclampsia. (AU)

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(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
LORENZON-OJEA, ALINE R.; YUNG, HONG WA; BURTON, GRAHAM J.; BEVILACQUA, ESTELA. The potential contribution of stromal cell-derived factor 2 (SDF2) in endoplasmic reticulum stress response in severe preeclampsia and labor-onset. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, v. 1866, n. 2, . (16/04210-8, 17/06824-6, 14/13052-1)
LORENZON, ALINE R.; MORELI, JUSCIELE BROGIN; MELO, RAFAELA DE MACEDO; NAMBA, FELIPE YUKIO; STAFF, ANNE CATHRINE; YUNG, HONG WA; BURTON, GRAHAM J.; BEVILACQUA, ESTELA. Stromal Cell-Derived Factor (SDF) 2 and the Endoplasmic Reticulum Stress Response of Trophoblast Cells in Gestational Diabetes Mellitus and In vitro Hyperglycaemic Condition. CURRENT VASCULAR PHARMACOLOGY, v. 19, n. 2, p. 201-209, . (16/04210-8, 14/13052-1, 17/06824-6)
BATTAGELLO, DANIELLA S.; LORENZON, ALINE R.; DINIZ, GIOVANNE B.; MOTTA-TEIXEIRA, LIVIA C.; KLEIN, MARIANNE O.; FERREIRA, JOZELIA G. P.; ARIAS, CARLOS M.; ADAMANTIDIS, ANTOINE; SITA, V, LUCIANE; CIPOLLA-NETO, JOSE; et al. The Rat Mammary Gland as a Novel Site of Expression of Melanin-Concentrating Hormone Receptor 1 mRNA and Its Protein Immunoreactivity. FRONTIERS IN ENDOCRINOLOGY, v. 11, . (15/05990-4, 16/02748-0, 17/16293-8, 10/52068-0, 16/04210-8, 17/17998-5, 14/50457-0, 12/04554-8, 14/13052-1, 16/18941-4, 16/19845-9, 16/02224-1)

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