Study of the induction of regulatory microRNAs by TNP dependent on Aryl hydrocarbon Receptor (AhR) activation

• Grant number: 19/27677-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2020
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Immunology - Immunogenetics
• Principal Investigator: Monica Valdyrce dos Anjos Lopes Ferreira
• Grantee: Geonildo Rodrigo Disner
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling, AP.CEPID
• Associated scholarship(s): 21/08411-6 - Delineating physiological and toxic impact of TnP on aryl hydrocarbon receptor (AhR) signaling through morphometric and transcriptomic profiling using the zebrafish embryo model, BE.EP.PD

Abstract

The mission of the Platforma Zebrafish of the Butantan Institute - Applied Toxinology Laboratory is to use toxins as molecular tools for the study of regulatory mechanisms that control inflammation. In the Immune Regulation Unit, the study of venomous fish had started and a new family of Natterine toxins was discovered, as well as the novel TnP peptide with anti-inflammatory activity from the poison of the Brazilian fish Thalassophryne nattereri. Investigate the response profile of various elements that control protein transcription is one of the potential biomarkers of biological changes resulting from exposure to toxins. Thus, we focus on this study the AhR-Aryl Hydrocarbon Receptor, which is a known ligand-dependent transcription factor known for its response to environmental pollutants. Although there is much knowledge about the toxicological action of AhR in response to PAHs and PCDDs, little is known about the physiological role of AhR, which can regulate multiple signaling pathways, development, immune homeostasis, cell death, inflammation, and induce over-regulation of miRNA to inhibit carcinogenesis. Recently, AhR has emerged as a suppressor of inflammation, oxidative stress, and apoptosis through mechanisms that may involve the regulation of non-coding microRNAs. Therefore, this study aims to use Zebrafish as a model organism to investigate the role of the transcription factor AhR in regulating miRNA expression in response to TnP treatment and adjacent cellular and molecular mechanisms. Our hypothesis is that TnP activates the AhR receptor, which in turn undergoes cytosol translocation to the nucleus. Next, miRNAs can be produced leading to repression of inflammatory genes, induced by LPS treatment. A better understanding of the mechanisms that regulate acute inflammatory events may lead us to the development of new therapeutic and more efficient strategies, besides contributing to the understanding of molecular mechanisms underlying this possible form of treatment involving the peptide TnP. (AU)

Scientific publications

(5)

(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)

LIMA, CARLA; DISNER, GEONILDO RODRIGO; FALCAO, MARIA ALICE PIMENTEL; SENI-SILVA, ANA CAROLINA; MALESKI, ADOLFO LUIS ALMEIDA; SOUZA, MILENA MARCOLINO; REIS TONELLO, MAYARA CRISTINA; LOPES-FERREIRA, MONICA. The Natterin Proteins Diversity: A Review on Phylogeny, Structure, and Immune Function. TOXINS, v. 13, n. 8, AUG 2021. (13/07467-1, 19/27677-7, 19/02333-3)

LIMA, CARLA; PIMENTEL FALCAO, MARIA ALICE; SANTOS ROSA, JOAO GABRIEL; DISNER, GEONILDO RODRIGO; LOPES-FERREIRA, MONICA. Pesticides and Their Impairing Effects on Epithelial Barrier Integrity, Dysbiosis, Disruption of the AhR Signaling Pathway and Development of Immune-Mediated Inflammatory Diseases. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 20, p. 19-pg., 2022-10-01. (21/06084-8, 19/27677-7, 21/08891-8, 13/07467-1)

DISNER, GEONILDO R.; FALCAO, MARIA A. P.; LIMA, CARLA; LOPES-FERREIRA, MONICA. In Silico Target Prediction of Overexpressed microRNAs from LPS-Challenged Zebrafish (Danio rerio) Treated with the Novel Anti-Inflammatory Peptide TnP. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 13, JUL 2021. (13/07467-1, 19/27677-7)

DISNER, GEONILDO RODRIGO; FALCAO, MARIA ALICE PIMENTEL; LIMA, CARLA; LOPES-FERREIRA, MONICA. Zebrafish Beyond the Bench: The 'Plataforma Zebrafish Open Doors' Programme. ATLA-ALTERNATIVES TO LABORATORY ANIMALS, v. 49, n. 5, p. 7-pg., 2021-09-01. (19/27677-7, 18/17413-0, 13/07467-1)

DISNER, GEONILDO RODRIGO; LOPES-FERREIRA, MONICA; LIMA, CARLA. Where the Aryl Hydrocarbon Receptor Meets the microRNAs: Literature Review of the Last 10 Years. FRONTIERS IN MOLECULAR BIOSCIENCES, v. 8, p. 13-pg., 2021-10-21. (19/27677-7, 13/07467-1)