The role of Septin 9 in regulating vascular permeability regulation in malarial respiratory distress syndrome

Malaria is a huge public health problem worldwide and has caused 409,000 deaths in 2019. Its severe form can manifest in the lungs, a disease known as acute respiratory distress syndrome (ARDS). Not much is known on the development of malaria-associated ARDS (MA-ARDS), especially regarding the mechanisms of increased vascular permeability. Previously, established a murine model with DBA/2 mice infected with Plasmodium berghei ANKA that mimics several aspects of human ARDS, such as pulmonary edema, hemorrhages, pleural effusion and hypoxemia. Results from previous studies in vitro pointed to an increase in vascular permeability when Infected erythrocytes come into contact with endothelial cells via activation of RhoA and alteration of the FAK. Recently, using a proteomic discovery strategy observed the overexpression of 32 proteins in the lung tissue of mice DBA/2 infected with P. berghei ANKA who developed ARDS, and among them, the Septin 9. How does this protein promote cytoskeletal rearrangements and cell turnover? focal adhesions by targeting Rho/ROCK and FAK signaling, we hypothesize that the Septin 9 may be a key molecule for increasing vascular permeability in malaria-associated ARDS. Therefore, if this hypothesis is confirmed, the intervention this signaling pathway could help patients not to develop severe malaria.

Project details

Basic Science

Oct 2021

Brazil