Characterization of the expression of genes MyoD, PAX7 and Dapper1 during the regeneration of skeletal muscle of mice after injection of Bothrops venom

Abstract

In general, the accidents caused by Bothrops snakes affect the skin and muscular soft tissues of the inferior limbs of the victims. The botropic venom presents myotoxic, hemorrhagic and proteolytic effects that are widely known. Experimental data show that the local alterations caused by venom develop very fast due both to a direct action of myotoxins and indirectly by tissue anoxia caused by the action of the hemorrhagic toxins in the microcirculation, both present in the venom. As a result, muscle tissue undergoes a catabolic phase which is accompanied by local edema and intense inflammatory response, where proinflammatory cytokines, such as TNF-±, IFN-³ and IL-1² are released by neutrophil and macrophage inflammatory infiltrate. Thereafter and depending on the damage extension, the muscle tissue starts a regeneration process, whose onset starts generally 72 hours after damage. Regeneration will require the activation of undifferentiated satellite cells that are quiescent between the basal membrane and the muscle fiber sarcolemma. Among the molecules involved in the satellite cell activity is the transcriptional factor paired-box Pax7. In addition, myogenic regulatory factors, which include MyoD, Myogenin, Myf-5 and MRF-4, are responsible for the control of the developmental and regulatory myogenesis. It is suspected that the gene that codifies the adaptor protein Dapper1 (Dpr1) is also expressed during the skeletal muscle regeneration, since it is intensely expressed in the somites, in muscle precursor cells.In this context, the purpose of this work is to characterize the expression of the genes MyoD, Pax7 and Dpr1 in mice skeletal muscle after intoxication by Bothrops jararacussu (jararacuçu) venom. The characterization of the expression of genes that regulate the post-developmental myogenesis (reparative myogenesis) is an interesting strategy to amplify the knowledge about the mechanisms involved in the post-injury reparative process of muscular tissue, for example caused by botropic venom. This work may allow the comparison with the mechanisms that are active during the embrionary myogenesis and will be useful for developing interventional therapies after skeletal tissue damage. This kind of approach is new and has relevance in public health. (AU)