Effect of annexin A1 and its mimetic peptides in models of inflammatory response in vitro (2D and 3D) and acute toxicity in vivo

• Grant number: 20/03565-2
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2020
• End date: July 31, 2022
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Cristiane Damas Gil
• Grantee: Cristiane Damas Gil
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Karin Vicente Greco

Abstract

Annexin A1 (AnxA1) is a 37 kDa protein capable of regulating various cellular and molecular stages of the inflammatory response and is involved in endogenous mechanisms that are activated to obtain an adequate resolution. In addition, some synthetic peptides derived from the N-terminal domain of AnxA1 mimic the pharmacological property of the total protein, especially its anti-inflammatory activity, binding to a specific class of transmembrane receptors coupled to G protein, the formyl peptide receptors (FPRs). However, the molecular mechanisms by which this protein and its peptides modulate cellular responses, particularly in inflammatory bowel diseases and neuroinflammation, are not yet fully determined. Regarding gastrointestinal diseases, many recent advances have contributed to the understanding of its pathophysiology, however, in vitro models using cell culture as an alternative need to be improved in order to study new targets in inflammation and explore new treatments. In this context, organoid units (OUs) are an interesting alternative, representing self-organizing and self-renewing 3D structures composed of a cluster of different cells in vitro that resemble their original organ in architecture and function. These OUs can be used to (i) understand the intrinsic tissue repair mechanisms to try to promote healthy regeneration and reduce pathological wound healing responses; (ii) studying alternatives to treat chronic inflammatory diseases, or (iii) as a screening model to explore alternative therapies, reducing the need to use a larger number of animals. We also emphasize that AnxA1, in addition to mediating inflammation, is involved in important pathophysiological roles including cell proliferation and protection against DNA damage, suggesting a regulatory role in oxidative stress associated with toxicity induced by chemical agents or inflammation. Thus, we will evaluate the role of the AnxA1 protein and its mimetic peptides in experimental models in vitro (2D and 3D) of inflammation and in vivo of acute toxicity. Thus, different methodologies will be used, such as: histological analysis, immunohistochemistry, immunofluorescence, Elisa, western blotting, lipidomics, eicosanomics, electron microscopy, among others, which will enable the understanding of the mechanisms of action of this protein and its peptides, as well as their possible therapeutic applications. (AU)

Scientific publications

(7)

(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)

LICE, IZABELLA; SANCHES, JOSE MARCOS; CORREIA-SILVA, REBECA D.; CORREA, MAB P.; ICIMOTO, MARCELO Y.; SILVA, ALEX A. R.; SANCHEZ-VINCES, SALVADOR; PORCARI, ANDREIA M.; MOREIRA, VANESSA; GIL, CRISTIANE D.. ffects of Formyl Peptide Receptor Agonists Ac9-12 and WKYMV in In Vivo and In Vitro Acute Inflammatory Experimental Model. CELLS, v. 11, n. 2, JAN 2022. (19/15017-2, 20/03565-2, 19/04314-6)

SANCHES, JOSE MARCOS; CORREIA-SILVA, REBECA D.; DUARTE, GUSTAVO H. B.; FERNANDES, ANNA MARIA A. P.; SANCHEZ-VINCES, SALVADOR; CARVALHO, PATRICIA O.; OLIANI, SONIA M.; BORTOLUCI, KARINA R.; MOREIRA, VANESSA; GIL, CRISTIANE D.. Role of Annexin A1 in NLRP3 Inflammasome Activation in Murine Neutrophils. CELLS, v. 10, n. 1, JAN 2021. (20/03565-2, 19/19949-7)

LUCCHI, DANILO B. M.; SASSO, GISELA R. S.; SENA, LETICIA S.; SANTOS, DIEGO D.; FRANCO, PAULO C.; LICE, IZABELLA; BORGES, FERNANDA T.; OLIANI, SONIA M.; GIL, CRISTIANE D.. The role of annexin A1-derived peptide Ac2-26 on liver and kidney injuries induced by cisplatin in rats. Life Sciences, v. 304, p. 10-pg., 2022-09-01. (19/14331-5, 19/19949-7, 20/03565-2)

SENA, LETICIA S.; SASSO, GISELA R. S.; SANCHES, JOSE MARCOS; FRANCO, PAULO C.; AZEVEDO, MARISA F.; OLIANI, SONIA M.; GIL, CRISTIANE D.. Pharmacological treatment with annexin A1-derived peptide protects against cisplatin-induced hearing loss. Toxicology Letters, v. 363, p. 9-pg., 2022-05-24. (19/19949-7, 20/03565-2)

SANTOS, DIEGO D.; SASSO, GISELA R. S.; BELOTE, NYCOLE M.; DA SILVA, RAFAEL ANDRE; LICE, IZABELLA; CORREIA-SILVA, REBECA D.; BORGES, FERNANDA T.; CARBONEL, ADRIANA A. F.; GIL, CRISTIANE D.. Galectin-3 is a key hepatoprotective molecule against the deleterious effect of cisplatin. Life Sciences, v. 318, p. 10-pg., 2023-02-17. (20/03565-2)

SANCHES, JOSE MARCOS; ROSSATO, LUANA; LICE, IZABELLA; ALVES DE PILOTO FERNANDES, ANNA MARIA; BUENO DUARTE, GUSTAVO HENRIQUE; ROSINI SILVA, ALEX APARECIDO; PORCARI, ANDREIA DE MELO; CARVALHO, PATRICIA DE OLIVEIRA; GIL, CRISTIANE DAMAS. he role of annexin A1 in Candida albicans and Candida auris infections in murine neutrophil. Microbial Pathogenesis, v. 150, JAN 2021. (20/03565-2)

SANCHES, JOSE MARCOS; ROSSATO, LUANA; LICE, IZABELLA; ALVES DE PILOTO FERNANDES, ANNA MARIA; BUENO DUARTE, GUSTAVO HENRIQUE; ROSINI SILVA, ALEX APARECIDO; PORCARI, ANDREIA DE MELO; CARVALHO, PATRICIA DE OLIVEIRA; GIL, CRISTIANE DAMAS. The role of annexin A1 in Candida albicans and Candida auris infections in murine neutrophils. Microbial Pathogenesis, v. 150, p. 8-pg., 2021-01-01. (20/03565-2)