The role of septin 9 in the regulation of vascular permeability in malaria-associated acute respiratory distress syndrome

• Grant number: 22/08582-8
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): November 01, 2022
• Effective date (End): September 30, 2023
• Field of knowledge: Biological Sciences - Parasitology
• Principal Investigator: Sabrina Epiphanio
• Grantee: Stefani Aparecida Minchio Rodrigues
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Malaria is a huge public health problem worldwide and 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 about the development of malaria-associated ARDS (MA-ARDS), especially regarding the mechanisms of increased vascular permeability. Previously, we established a murine model with Plasmodium berghei ANKA-infected DBA/2 mice that mimics several aspects of human ARDS, such as pulmonary edema, hemorrhages, pleural effusion and hypoxemia. Our previous in vitro results pointed to an increase in vascular permeability when infected erythrocytes come into contact with endothelial cells via RhoA activation and FAK alteration. Recently, using a proteomic discovery strategy, we observed the overexpression of 32 proteins in the lung tissue of DBA/2 mice infected with P. berghei ANKA that developed ARDS, and among them, Sep-tin 9. As this protein promotes cytoskeletal rearrangements and turnover of focal adhesions by directing Rho/ROCK and FAK signaling, we hypothesized that Septin 9 could be a key molecule for increased vascular permeability in SRDA associated with malaria. Therefore, if this hypothesis is confirmed, intervention in this signaling pathway could help patients not to develop severe malaria.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

RODRIGUES, Stefani Aparecida Minchio. The role of Septin 9 in regulating vascular permeability in malarial respiratory distress syndrome. 2024. Master's Dissertation - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.