Omentum acts as a regulatory organ controlling skeletal muscle repair of mdx mice diaphragm

  • Douglas Florindo Pinheiro
  • Rafael F. da Silva
  • Thiago Morais Barbosa
  • Jaciara F. G. Gama
  • Aline C. Gomes
  • Thereza Quirico-Santos
  • Jussara Lagrota-CandidoEmail author
Regular Article


Duchenne muscular dystrophy is a lethal X-linked muscle wasting disease due to mutations of the dystrophin gene leading to distinct susceptibility to degeneration and fibrosis among skeletal muscles. This study aims at verifying whether intense mdx diaphragm remodeling could be attributed to influences from the omentum, a lymphohematopoietic tissue rich in progenitor cells and trophic factors. Mdx omentum produces growth factors HGF and FGF and increased amounts of VEGF with pleiotropic actions upon muscular progenitors and myoblast differentiation. Histology revealed that the absence of the omentum reduced inflammation and collagen deposition in the diaphragm. The diaphragm from omentectomized mdx mice presents impaired repair with a predominance of collagen type I deposition, decreased muscle regeneration and a reduction in collagen type IV and indication of altered basal lamina integrity in the diaphragm. Omentectomy further reduced inflammatory infiltration and NFκ-B activation but a change in the pattern of muscle inflammation with low numbers of the F4/80+CD206+ M-2 macrophage subset. Although omentectomized mice had high levels of Pax7, myogenin and TNF-α, the percentage of myofibers undergoing regeneration was low thus suggesting that a lack of the omentum halts the muscle differentiation program. Such results support that omentum exerts a regulatory function inducing an inflammatory process that favors regeneration and inhibits fibrosis selectively in the diaphragm muscle thus being a potential site for therapeutic interventions in DMD.


Omentum mdx Macrophages Fibrosis Diaphragm Muscle regeneration 



We are grateful to Nina Cortez and Diogo G. Garcia for technical assistance and Giselle M. Faria with the statistical analysis.

Funding information

This study was financed in part by FAPERJ (Fundação de Amparo a Pesquisa do Rio de Janeiro), PROPPI (UFF) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001.

Supplementary material

441_2019_3012_Fig6_ESM.png (2 mb)
Figure S1

Gastrocnemius muscle from mdx at 12 weeks old is not affected by omentectomy. Sirius Red stain of gastrocnemius muscle and respective quantification of area occupied by collagen and regenerating myofibres from SHAM and OTX mdx mice at 12 (a) and 24 weeks old (b). (PNG 2026 kb)

441_2019_3012_MOESM1_ESM.tif (8.8 mb)
High-resolution Image (TIF 8991 kb)
441_2019_3012_Fig7_ESM.png (94 kb)
Figure S2

Measurements of TNF-α and myogenin by real-time PCR in OTX mdx gastrocnemius at 12 and 24 weeks old. Test samples were normalized against the mRNA levels detected for the beta-actin gene and expressed as fold change compared to SHAM. (*p < 0.05) (PNG 93 kb)

441_2019_3012_MOESM2_ESM.tif (588 kb)
High-resolution Image (TIF 587 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Douglas Florindo Pinheiro
    • 1
  • Rafael F. da Silva
    • 1
  • Thiago Morais Barbosa
    • 1
  • Jaciara F. G. Gama
    • 1
  • Aline C. Gomes
    • 2
  • Thereza Quirico-Santos
    • 2
  • Jussara Lagrota-Candido
    • 1
    Email author
  1. 1.Departamento de Imunobiologia, Instituto de BiologiaUniversidade Federal FluminenseNiteróiBrazil
  2. 2.Departamento de Biologia Celular e Molecular, Instituto de BiologiaUniversidade Federal FluminenseNiteróiBrazil

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