Phosphorylation and cleavage profiles of proteins related to intracellular signaling key pathways in menstrual blood-derived mesenchymal stem cells from women with and without endometriosis

• Grant number: 23/09461-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2023
• End date: September 30, 2024
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Juliana Meola Lovato
• Grantee: Letícia Lorenzi
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Background: Endometriosis is a public health problem with a complex and multifactorial etiopathogenesis that involves aberrant biological processes, such as (1) retrograde menstruation, lymphovascular dissemination, or metaplasia; (2) genetic predisposition and epigenetic events; (3) molecularly abnormal endometrial cells; (4) altered microenvironment (hormonal, inflammatory and pro-oxidant); and (5) participation of menstrual flow mesenchymal stem cells (MenSCs) with morphological, phenotypic and functional modifications. Recent data from our group indicate alterations related to the modulation of signaling pathways in endometriosis MenSCs. In this study, we sought to understand the differential activation of these intracellular signaling pathways, responsible for cell proliferation and growth processes, response to environmental stress and DNA damage, apoptosis, and cycle control. The data that will be obtained may contribute to understanding the role of MenSCs in the etiopathogenesis of endometriosis and will guide research in regenerative medicine and cell therapy. Objective: To compare the control and endometriosis groups regarding the intensity of signaling proteins phosphorylation or cleavage: ERK1/2, STAT1, STAT3, AKT, AMPK±, RPS6 (ribosomal protein S6), MTOR, HSP27, BAD, RPS6KB1 (p70- S6K), PRAS40, TP53, p38 (MAPK), SAPK/JNK, PARP, CASP3 (caspase 3) and GSK3². Study Design: A case-control study. Methods: MenSCs from the biorepository will be used for total protein extraction and evaluation of phosphorylation and cleavage, using an antibody array, of the 18 molecules mentioned above, in samples from women with (n=10) and without endometriosis (n=10). The data obtained will be quantified and statistically analyzed.