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

• Grant number: 23/05478-8
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2023
• End date: November 30, 2025
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Sabrina Epiphanio
• Grantee: Sabrina Epiphanio
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Carla Claser ; Cláudio Romero Farias Marinho ; Giuseppe Palmisano ; Lívia Rosa Fernandes ; Silvia Vilar Portugal

Abstract

Malaria remains a significant public health problem worldwide, and it is present in 84 countries where malaria is endemic. In 2021 this critical parasitic disease caused 619,000 deaths. Acute respiratory distress syndrome (ARDS) is a form of severe malar-ia that leads to death in infected patients. However, to this day, there are still many gaps in the understanding of malaria-associated ARDS, especially concerning the switch to increased vascular permeability. Our previous in vitro results showed that cytoadhesion of infected red blood cells in contact with endothelial cells promotes cytoskeletal alteration and increased vascular permeability via RhoA activation and FAK modification. Using a proteomic discovery strategy, we recently observed 1414 proteins common to the lungs of controlled and infected mice, while 32 proteins were overexpressed only in P. berghei ANKA-infected DBA/2 mice that developed ARDS on the 7 and 9 days post-infection. Among these proteins, overexpression of septin 9 was observed. As septins are considered the fourth element of the cytoskeleton and, especially, septin 9 was involved in promoting cytoskeletal rearrangements and turnover of focal adhesions by directing Rho/ROCK and FAK signaling, we hypothesize that septin 9 may play an essential role in the pathogenesis of malaria-associated ARDS. Therefore, validation of septin 9 expression is essential, and if our hypothesis is confirmed, intervention in this signaling pathway could help patients not to develop severe malaria. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LOHMANN-MENEZES, BRUNA; GIAROLLA, JEANINE; DA SILVA-SANTOS, YASMIN; PETRI, GIULIANA; EPIPHANIO, SABRINA. Canis lupus familiaris and diclofenac: understanding the potential risks of this association. FRONTIERS IN VETERINARY SCIENCE, v. 11, p. 6-pg., 2024-12-09. (23/05478-8)

ROSA-FERNANDES, LIVIA; SANTIAGO, VERONICA FEIJOLI; SILVA-SANTOS, YASMIN DA; LOPES, TISSIANE TAROSSO; PEIXOTO, ERIKA PAULA MACHADO; RODRIGUES, STEFANI APARECIDA MINCHIO; MARINHO, CLAUDIO ROMERO FARIAS; PALMISANO, GIUSEPPE; EPIPHANIO, SABRINA. Serum Proteomics of Experimental Malaria-Associated ARDS Reveals a Regulation of Acute-Phase Response Proteins. JOURNAL OF IMMUNOLOGY RESEARCH, v. 2025, n. 1, p. 13-pg., 2025-01-01. (20/03163-1, 18/15549-1, 22/08582-8, 20/04923-0, 20/06747-4, 23/05478-8, 22/13150-0, 18/20468-0)

SILVA-SANTOS, YASMIN; PAGNI, ROBERTA LIBERATO; GAMON, THAIS HELENA MARTINS; DE AZEVEDO, MARCELA SANTIAGO PACHECO; BIELAVSKY, MONICA; DARIDO, MARIA LAURA GOUSSAIN; DE OLIVEIRA, DANIELLE BRUNA LEAL; DE SOUZA, EDMARCIA ELISA; WRENGER, CARSTEN; DURIGON, EDSON LUIZ; et al. Lisinopril increases lung ACE2 levels and SARS-CoV-2 viral load and decreases inflammation but not disease severity in experimental COVID-19. FRONTIERS IN PHARMACOLOGY, v. 15, p. 14-pg., 2024-07-12. (20/06409-1, 15/26722-8, 23/05478-8, 20/06747-4, 22/13150-0, 20/12277-0)