EFFECTS OF EXOGENOUS GHRELIN ON MYOGENIC REGULATION, INFLAMMATION AND MUSCLE FIBROSIS IN MDX MICE

• Grant number: 25/06515-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2025
• End date: May 31, 2027
• Field of knowledge: Biological Sciences - Morphology
• Principal Investigator: Flávia de Oliveira
• Grantee: Pietra Mascarenhas Souza Costa
• Host Institution: Pró-Reitoria de Pós-Graduação e Pesquisa. Universidade Federal de São Paulo (UNIFESP). São Paulo , SP, Brazil

Abstract

ABSTRACTBackground: Duchenne muscular dystrophy (DMD) is a serious disease, characterizedby progressive loss of muscle tissue due to the degradation of myofibers. Ghrelin has shownpromising potential effects in treating the consequences of DMD, but it has been limitedlystudied in mdx mice and comprehensive pre-clinical studies are still required to understandthe impact of exogenous ghrelin administration in the advanced stages of DMD. Aim:Evaluate the effects of exogenous ghrelin on muscle degeneration/regeneration, myogenesis,atrophy, inflammation, and fibrosis in mdx mice in the phase of already established histopathological changes in DMD. Method: Sixteen-week-old C57BL/10-DMD mdx and C57BL/10J male mice will be distributed into four groups (n=10): C57BL/10Juntreated (Ctl), C57BL/10-DMD mdx untreated (Mdx), C57BL/10J ghrelin-treated (Ctl-Gre),and C57BL/10-DMD mdx ghrelin-treated (Mdx-Gre). The experimental design will last eightweeks, and the Ctl-Gre and Mdx-Gre groups will be treated with 320 µl/kg/day of ghrelin viasubcutaneous injection for six days a week. The Ctl and Mdx groups will follow the sameprotocol but will receive saline solution intead. The gastrocnemius muscle will be analyzedfor histopathological parameters (degeneration-inflammation area, regeneration,inflammatory infiltrate, collagen types I and III), morphometric analysis of muscle fibers,immunohistochemical biomarkers (MyoD, Myogenin, Pax 7 and COX-2) and mRNA geneexpression analysis of MuRF1, MAFbx, IGF-1 and TNF-¿. Expected results: Ghrelin couldinfluence inflammation and, consequently, ameliorate fibrosis, atrophy and myogenesis in themuscles of mdx mice.