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Mechanisms of action of omega-3 and omega-6 in the tissue repair process: neuro-immune focus

Grant number: 13/06810-4
Support type:Research Grants - Young Investigators Grants
Duration: February 01, 2014 - January 31, 2019
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Hosana Gomes Rodrigues
Grantee:Hosana Gomes Rodrigues
Home Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
Assoc. researchers:Augusto Ducati Luchessi ; Marco Aurélio Ramirez Vinolo ; Maria Cláudia Gonçalves de Oliveira Fusaro ; Rui Curi
Associated grant(s):14/15127-9 - Multiuser equipment approved in grant 2013/06810-4: flow citometry BD Accury, AP.EMU
Associated scholarship(s):17/26366-2 - Influence of the inflammatory response on the extracellular matrix composition during the wound healing in fat-1 mice, BP.DR
18/00529-5 - Effects of eicosapentaenoic omega-3 fatty acid (EPA) supplementation on wound healing in diabetic mice: focus on the NLRP3 pathway, BP.MS
17/12025-9 - Investigation of spleen participation in the cholinergic anti-inflammatory pathway during the wound healing process in mice, BP.IC
+ associated scholarships 16/15955-4 - Effects of linoleic acid on in vitro modulation of angiogenesis process, BP.MS
16/02021-3 - Wound healing in fat -1 mice: involvement of anti- inflammatory cholinergic pathway, BP.MS
15/17522-5 - Effects of oral administration of the linoleic (la) fatty acid on the wound healing process in diabetic mice, BP.IC
14/03500-7 - The wound healing process in fat-1 mice: crosstalk between neurons and macrophages in the context of wounds, BP.IC - associated scholarships

Abstract

In the evolutionary process, the ability to repair damage has become essential for organisms survival. The skin is a protective barrier constantly renewed. If this barrier is breached by an injury or infection, a rapid repair program is activated. This program is known as healing or tissue repair, consists of three interdependent and concurrent phases: the early inflammatory phase (lasting from minutes to days), the proliferative phase (days to weeks) and the remodeling phase (lasting from weeks to months). Though essential for the initiation of repair, exacerbated inflammatory response, prolonged or inappropriate can cause even more damage to the body. Thus, knowledge of the mechanisms governing this response is essential for the resolution of wound healing. Fatty acids play different roles in cells besides being used as energetic substrates. Some are embedded in cell membranes, are involved in intracellular signaling, influence the activity of transcription factors and the expression of many genes and are precursors of the synthesis of eicosanoids (such as arachidonic acid and eicosapentaenoic acid) and may then regulate the inflammatory response. Currently, it has been described that the central nervous system (CNS) plays a key role in regulating inflammation. According to some studies, the change in consumption of certain lipids can, throug the cholinergic pathway, assist in the resolution of inflammatory phase, present during the healing process of wounds. Thus, our goal is to investigate the mechanisms by which linoleic acid facilitates and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) hinder the resolution of wound healing. Our hypothesis is based on the essentiality of the inflammatory response to tissue regeneration process. We believe that these fatty acids modulate the inflammatory phase, acting on the cells of the immune system, inducing / inhibiting the production of inflammatory mediators and that the vagal innervation of the skin is one of the means by which these fatty acids exert their functions. (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)
CANDREVA, THAMIRIS; KUHL, CAROLINA M. C.; BURGER, BEATRIZ; DOS ANJOS, MARIAH B. P.; TORSONI, MARCIO A.; CONSONNI, SILVIO R.; CRISMA, AMANDA R.; FISK, HELENA L.; CALDER, PHILIP C.; DE MATO, FELIPE C. P.; SERNAGLIA, ERICA M.; VINOLO, MARCO A. R.; RODRIGUES, HOSANA G. Docosahexaenoic acid slows inflammation resolution and impairs the quality of healed skin tissue. Clinical Science, v. 133, n. 22, p. 2345-2360, NOV 2019. Web of Science Citations: 0.
ANTUNES, KRIST HELEN; FACHI, JOSE LUIS; DE PAULA, ROSEMEIRE; DA SILVA, EMANUELLE FRAGA; PRAL, LAIS PASSARIELLO; DOS SANTOS, ADARA AUREA; MALAQUIAS DIAS, GREICY BRISA; VARGAS, JOSE EDUARDO; PUGA, RENATO; MAYER, FABIANA QUOOS; MAITO, FABIO; ZARATE-BLADES, CARLOS R.; AJAMI, NADIM J.; ST ANA, MARCELLA RAMOS; CANDREVA, THAMIRIS; RODRIGUES, HOSANA GOMES; SCHMIELE, MARCIO; PEDROSA SILVA CLERICI, MARIA TERESA; PROENCA-MODENA, JOSE LUIZ; VIEIRA, ANGELICA THOMAS; MACKAY, CHARLES R.; MANSUR, DANIEL; CABALLERO, MAURICIO T.; MARZEC, JACQUI; LI, JIANYING; WANG, XUTING; BELL, DOUGLAS; POLACK, FERNANDO P.; KLEEBERGER, STEVEN R.; STEIN, RENATO T.; RAMIREZ VINOLO, MARCO AURELIO; DUARTE DE SOUZA, ANA PAULA. Microbiota-derived acetate protects against respiratory syncytial virus infection through a GPR43-type 1 interferon response. NATURE COMMUNICATIONS, v. 10, JUL 22 2019. Web of Science Citations: 1.
BURGER, BEATRIZ; KUHL, CAROLINA M. C.; CANDREVA, THAMIRIS; CARDOSO, RENATO DA S.; SILVA, JESSICA R.; CASTELUCCI, BIANCA G.; CONSONNI, SILVIO R.; FISK, HELENA L.; CALDER, PHILIP C.; VINOLO, MARCO AURELIO R.; RODRIGUES, HOSANA G. Oral administration of EPA-rich oil impairs collagen reorganization due to elevated production of IL-10 during skin wound healing in mice. SCIENTIFIC REPORTS, v. 9, JUN 24 2019. Web of Science Citations: 1.
FACHI, JOSE LUIS; FELIPE, JAQUELINE DE SOUZA; PRAL, LAIS PASSARIELLO; DA SILVA, BRUNA KARADI; CORREA, RENAN OLIVEIRA; PEREIRA DE ANDRADE, MIRELLA CRISTINY; DA FONSECA, DENISE MORAIS; BASSO, PAULO JOSE; SARAIVA CAMARA, NIELS OLSEN; DE SALES E SOUZA, ERICKA LORENNA; MARTINS, FLAVIANO DOS SANTOS; SATO GUIMA, SUZANA EIKO; THOMAS, ANDREW MALTEZ; SETUBAL, JOAO CARLOS; MAGALHAES, YULI THAMIRES; FORTI, FABIO LUIS; CANDREVA, THAMIRIS; RODRIGUES, HOSANA GOMES; DE JESUS, MARCELO BISPO; CONSONNI, SILVIO ROBERTO; FARIAS, ALESSANDRO DOS SANTOS; VARGA-WEISZ, PATRICK; RAMIREZ VINOLO, MARCO AURELIO. Butyrate Protects Mice from Clostridium difficile-Induced Colitis through an HIF-1-Dependent Mechanism. CELL REPORTS, v. 27, n. 3, p. 750+, APR 16 2019. Web of Science Citations: 3.
SILVA, JESSICA R.; BURGER, BEATRIZ; KUHL, CAROLINA M. C.; CANDREVA, THAMIRIS; DOS ANJOS, MARIAH B. P.; RODRIGUES, HOSANA G. Wound Healing and Omega-6 Fatty Acids: From Inflammation to Repair. Mediators of Inflammation, 2018. Web of Science Citations: 6.
RODRIGUES, HOSANA G.; VINOLO, MARCO A. R.; SATO, FABIO T.; MAGDALON, JULIANA; KUHL, CAROLINA M. C.; YAMAGATA, ANA S.; PESSOA, ANA FLAVIA M.; MALHEIROS, GABRIELLA; DOS SANTOS, MARINILCE F.; LIMA, CAMILA; FARSKY, SANDRA H.; CAMARA, NIELS O. S.; WILLINER, MARIA R.; BERNAL, CLAUDIO A.; CALDER, PHILIP C.; CURI, RUI. Oral Administration of Linoleic Acid Induces New Vessel Formation and Improves Skin Wound Healing in Diabetic Rats. PLoS One, v. 11, n. 10 OCT 20 2016. Web of Science Citations: 8.
RODRIGUES, HOSANA G.; SATO, FABIO TAKEO; CURI, RUI; VINOLO, MARCO A. R. Fatty acids as modulators of neutrophil recruitment, function and survival. European Journal of Pharmacology, v. 785, p. 50-58, AUG 15 2016. Web of Science Citations: 20.

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