Impaired structural and functional regeneration of skeletal muscles from ß2-adrenoceptor knockout mice.

ABSTRACT

AIMS: ß2-adrenergic stimulation causes beneficial effects on structure and function of regenerating muscles; thus, the ß2-adrenoceptor may play an important role in the muscle regenerative process. Here, we investigated the role of the ß2 -adrenoceptor in skeletal muscle regeneration. METHODS: Tibialis anterior (TA) muscles from ß2-adrenoceptor knockout (ß2 KO) mice were cryolesioned and analysed after 1, 3, 10 and 21 days. The role of ß2-adrenoceptor on regenerating muscles was assessed through the analysis of morphological and contractile aspects, M1 and M2 macrophage profile, cAMP content, and activation of TGF-ß signalling elements. RESULTS: Regenerating muscles from ß2 KO mice showed decreased calibre of regenerating myofibres and reduced muscle contractile function at 10 days when compared with those from wild type. The increase in cAMP content in muscles at 10 days post-cryolesion was attenuated in the absence of the ß2 -adrenoceptor. Furthermore, there was an increase in inflammation and in the number of macrophages in regenerating muscles lacking the ß2-adrenoceptor at 3 and 10 days, a predominance of M1 macrophage phenotype, a decrease in TßR-I/Smad2/3 activation, and in the Smad4 expression at 3 days, while akirin1 expression increased at 10 days in muscles from ß2 KO mice when compared to those from wild type. CONCLUSIONS: Our results suggest that the ß2-adrenoceptor contributes to the regulation of the initial phases of muscle regeneration, especially in the control of macrophage recruitment in regenerating muscle through activation of TßR-I/Smad2/3 and reduction in akirin1 expression. These findings have implications for the future development of better therapeutic approaches to prevent or treat muscle injuries.