The regulation of Septin 9 in malaria-associated Acute Respiratory Distress Syndrome: from cytoadhesion to increased vascular permeability

Malaria continues to be an important public health problem throughout the world, it is present in 84 countries where malaria is endemic. In 2021, this important parasitic disease caused 619,000 deaths. Acute respiratory distress syndrome (ARDS) is a form of severe malaria that leads to death in infected patients. However, to this day there are still many gaps in the understanding of ARDS associated with malaria, especially regarding the mechanisms of increased vascular permeability. Previous in vitro results indicated that the cytoadhesion of infected erythrocytes in contact with endothelial cells promotes cytoskeletal alteration, increased vascular permeability, via RhoA activation and FAK modification. Recently, using a discovery proteomic strategy we observed 1414 proteins common to the lungs of control and infected mice, while 32 proteins were overexpressed only in P. berghei ANKA-infected DBA/2 mice that developed ARDS on days 7 and 9 post-infection. Among these proteins, overexpression of septin 9 was observed. As septins are considered the fourth element of the cytoskeleton and, especially, sep-tin 9 was involved in promoting cytoskeletal rearrangements and turnover of focal adhesions by directing Rho/ROCK signaling and FAK, it is hypothesized that septin 9 may have an important role in the pathogenesis of ARDS associated with malaria. Therefore, validating the expression of septin 9 is essential, and if the hypothesis is confirmed, intervention in this signaling pathway could help patients not develop severe malaria.

Project details

Basic Science

Sep 2023 — Aug 2025

Brazil