Evaluation of the effects of protein malnutrition and renutrition over the control of hematopoiesis: participation of class 3 and 4 semaphorins

Abstract

Protein malnutrition (DP) has a considerable presence in the world, with recent events favoring its increase in the world. DP causes various alterations in the physiological function of the organism, primarily affecting tissues with a high renewal rate, such as the hematopoietic tissue present inside the bone marrow, where the production of blood occurs through a process named hematopoiesis. Inside the bone marrow, the hematopoietic stem cell (CTH) interacts with other populations of cells and with soluble/transcriptional factors to guarantee the integrity of hematopoiesis. In this context, semaphorins (SEMAs), proteins initially characterized as actors in the nervous system, have been recognized as regulators of hematopoiesis. Among the existent subtypes of SEMAs, the literature highlights SEMAs of class 3 and 4 as regulators of hematopoietic populations, influencing the metabolism of the CTH while also regulating the bone marrow microenvironment. Considering that the CTH depends on the integrity of its surrounding microenvironment, DP considerably affects the hematopoietic process, with common findings involving anemia, leukopenia, molecular alterations in the CTHs, among others. Despite this, little is known about the reversibility of these changes after a process of renutrition, with data regarding how malnutrition and renutrition affects the hematopoietic regulatory function of SEMAs, including those behind the metabolic regulatory pathways involved in this process also being scarse. Therefore, this project aims to investigate the reversibility of the changes caused by DP in the bone marrow and in hematopoiesis using models of renutrition, while also investigating how DP and renutrition might affect the regulation of the bone marrow through class 3 and 4 SEMAs. (AU)