Expression of Sdf2 in human placenta from preeclamptic and gestational diabetic patients

• Grant number: 17/06824-6
• Support type: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): May 15, 2017
• Effective date (End): August 14, 2017
• Field of knowledge: Biological Sciences - Morphology
• Principal Investigator: Estela Maris Andrade Forell Bevilacqua
• Grantee: Aline Rodrigues Lorenzon
• Supervisor abroad: Graham J Burton
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Local de pesquisa : University of Cambridge, England
• Associated to the scholarship: 14/13052-1 - The role of Sdf2 (stromal cell derived factor 2) in cell survival/apoptosis of trophoblast cells via endoplasmic reticulum stress, BP.PD

Abstract

The stromal cell derived factor 2 (SDF2) was first described by Hamada et al. (1996); it is well conserved in mammals but its function is not fully understood. In human and mouse, SDF2 has a paralogous gene, SDF2L1 (78% similar in protein sequence). Human SDF2L1 is an endoplasmic reticulum-stress inducible-gene, whose function is related to quality control of new synthesized proteins. In Arabidopsis thaliana, SDF2-like (39% sequence identity) has also been implicated in quality control and activation of UPR in ER-stress. In a previous study, we show a close structural similarity of SDF2 with SDF2-like, its broad tissue distribution in mice and particularly in the human and murine placenta (Lorenzon-Ojea et al., 2014, 2016) and, its ultrastructural localization in the cisterns of the endoplasmic reticulum (Lorenzon-Ojea et al., 2014). We also verify the participation of SDF2 in ER stress in placental cells (human and mouse, trophoblast cells). When gene silencing assays was used for SDF2, we detected modifications in UPR cell survival/apoptosis markers (Lorenzon-Ojea et al., 2016). The activation and exacerbation of UPR has been described in several human pathologies, including gestational diseases such as preeclampsia and gestational diabetes. Preeclampsia is a multifactorial syndrome that affects 3-8% of pregnancies. It is associated with the development of hypertension, proteinuria, liver dysfunction and other systemic disturbances after 20 weeks of gestation. The most severe form of this syndrome (early onset) is associated with intrauterine growth restriction and high risk of maternal cardiovascular complications after delivery. Although the etiology is unclear, the placenta is widely recognized as a key factor for this syndrome.Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia, resulting from a defect in insulin action and/or production. In pregnancy, hyperglycemia poses both short-term and long-term risks to the health of women and their offspring, such as malformations, macrossomia, hypoxia and perinatal death. During adult life, such metabolic alterations increase the risk of metabolic, cardiovascular and malignant diseases.Whether SDF2 might also interfere in this signaling pathway in these pathologies is a particular aspect that merits further investigation. In this project, we proposed to examine whether SDF2 is associated with increased activation of placental ER stress and UPR in early onset preeclampsia and gestational diabetes.Stromal cell derived factor 2 (SDF2) protein expression will be assessed in chorionic villi from normal (healthy control), preeclampsia and gestational diabetes placentae from a preexistent tissue bank.