Pharmacological therapy of the dystrophinopathies: fibrosis and muscular regeneration in mdx mice treated with omega-3

• Grant number: 12/15492-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): October 01, 2012
• Effective date (End): July 31, 2016
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Maria Julia Marques
• Grantee: Samara Camaçarí de Carvalho
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The Duchenne Muscular Dystrophy (DMD) is the most severe of dystrophinopathies and results of non-expression of dystrophin in skeletal and cardiac muscle. The inflammatory response is exacerbated and seems to contribute to the progression of the disease leading to fibrosis and impairing muscle regeneration. In the dystrophic mice mdx distinct populations of macrophages (M1-M2-Th1 and Th2) influence respectively, muscle degeneration and regeneration regulating progression of the disease. M2 macrophages can activate myogenic cells, but its activity for a long time can promote fibrosis. In the absence of a cure for DMD, therapeutic intervention in inflammation, fibrosis and muscle regeneration can lead to significant improvements in health and longevity of the DMD patients. Recent studies in our laboratory showed that treatment with eicosapentaenoic acid (EPA) or capsules of omega-3 for a short time, decreases the dystrophic muscle necrosis as well as TNF-±, pro-inflammatory cytokine-related muscular degeneration. In the present study, we investigate the effects of prolonged use of omega-3 on inflammation, accumulation of fibrosis and regeneration in different muscles of mdx. We intend to deepen the knowledge about the mechanisms of action of the omega-3 in dystrophic muscle using histological, biochemical, molecular, and metabolomics, allowing the development of new therapies for DMD. (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)

DE CARVALHO, SAMARA CAMACARI; MATSUMURA, CINTIA YURI; NETO, HUMBERTO SANTO; MARQUES, MARIA JULIA. Identification of plasma interleukins as biomarkers for deflazacort and omega-3 based Duchenne muscular dystrophy therapy. CYTOKINE, v. 102, p. 55-61, FEB 2018. (12/15492-3, 14/04782-6, 13/00312-2)

FINKLER, JULIA M. G.; DE CARVALHO, SAMARA C.; NETO, HUMBERTO SANTO; MARQUES, MARIA J.. Cardiac and skeletal muscle changes associated with rosuvastatin therapy in dystrophic mdx mice. Anatomical Record-Advances in Integrative Anatomy and Evolutionary Biology, v. 303, n. 8, DEC 2019. (12/15492-3, 17/24051-4, 14/04782-6)

MARANHAO, JULIANA BARROS; MOREIRA, DRIELEN DE OLIVEIRA; MAURICIO, ADRIANA FOGAGNOLO; DE CARVALHO, SAMARA CAMACARI; FERRETTI, RENATO; PEREIRA, JULIANO ALVES; SANTO NETO, HUMBERTO; MARQUES, MARIA JULIA. Changes in calsequestrin, TNF-alpha, TGF-beta and MyoD levels during the progression of skeletal muscle dystrophy in mdx mice: a comparative analysis of the quadriceps, diaphragm and intrinsic laryngeal muscles. International Journal of Experimental Pathology, v. 96, n. 5, p. 285-293, OCT 2015. (12/03498-7, 12/13577-1, 12/15492-3, 14/04782-6)

DE CARVALHO, SAMARA CAMACARI; APOLINARIO, LETICIA MONTANHOLI; MICHELIN MATHEUS, SELMA MARIA; SANTO NETO, HUMBERTO; MARQUES, MARIA JULIA. EPA protects against muscle damage in the mdx mouse model of Duchenne muscular dystrophy by promoting a shift from the M1 to M2 macrophage phenotype. Journal of Neuroimmunology, v. 264, n. 1-2, p. 41-47, NOV 15 2013. (10/13412-7, 12/15492-3, 10/14750-3)

MAURICIO, ADRIANA FOGAGNOLO; DE CARVALHO, SAMARA CAMACARI; SANTO NETO, HUMBERTO; MARQUES, MARIA JULIA. Effects of dietary omega-3 on dystrophic cardiac and diaphragm muscles as evaluated by H-1 magnetic resonance spectroscopy: Metabolic profile and calcium-related proteins. CLINICAL NUTRITION ESPEN, v. 20, p. 60-67, AUG 2017. (12/13577-1, 12/15492-3, 14/04782-6)

Academic Publications

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

CARVALHO, Samara Camaçarí de. Pharmacological therapy of dystrophinopathies: fibrosis and muscular regeneration in mdx mice treated with omega-3. 2016. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.