Influence of HNF-4± on the Maintenance of Endoplasmic Reticulum Homeostasis of Pancreatic ² Cells

• Grant number: 22/11180-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2022
• End date: October 31, 2023
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Fernanda Ortis
• Grantee: Sabrina Taniguchi
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Diabetes mellitus (DM) is a group of diseases characterized by chronic hyperglycemia, whose incidence increases every year around the world. In different types of DM, there is a progressive dysfunction and loss of ² cells, resulting from different mechanisms. Among them, the main one is UPR (Unfolded Protein Response), an Endoplasmic Reticulum (ER) stress response that initially aims at restoring reticulum homeostasis through the activation of membrane proteins, IRE-1, PERK and ATF6 However, when activated for a long period of time, it can trigger apoptotic pathways. Previous studies suggest that the transcription factor HNF-4± exerts antagonistic effects on the modulation of UPR pathways. While a mutation in HNF-4± results in an increased ER stress susceptibility, the lack of HNF-4± is associated with a decrease of ER stress susceptibility. Thus, for a better understanding of the influence of HNF-4± in the modulation of UPR, the purpose of this work is to evaluate the expression of ER stress marker proteins in INS-1E cells treated with pro-inflammatory cytokines, in the presence and in the absence of HNF-4±, through silencing with specific siRNA. Understanding this influence is extremely relevant for the development of prophylactic and cure therapies for DM.