Abstract
BackgroundThe signal transducer and activator of transcription 6 (STAT6) transcription factor plays a vitally important role in immune cells, where it is activated mainly by interleukin-4 (IL-4). Because IL-4 is an essential cytokine for myotube formation, STAT6 might also be involved in myogenesis as part of IL-4 signaling. This study was conducted to elucidate the role of STAT6 in adult myogenesis in vitro and in vivo.MethodsMyoblasts were isolated from male mice and were differentiated on a culture dish to evaluate the change in STAT6 during myotube formation. Then, the effects of STAT6 overexpression and inhibition on proliferation, differentiation, and fusion in those cells were studied. Additionally, to elucidate the myogenic role of STAT6 in vivo, muscle regeneration after injury was evaluated in STAT6 knockout mice.ResultsIL-4 can increase STAT6 phosphorylation, but STAT6 phosphorylation decreased during myotube formation in culture. STAT6 overexpression decreased, but STAT6 knockdown increased the differentiation index and the fusion index. Results indicate that STAT6 inhibited myogenin protein expression. Results of in vivo experiments show that STAT6 knockout mice exhibited better regeneration than wild-type mice 5 days after cardiotoxin-induced injury. It is particularly interesting that results obtained using cells from STAT6 knockout mice suggest that this STAT6 inhibitory action for myogenesis was not mediated by IL-4 but might instead be associated with p38 mitogen-activated protein kinase phosphorylation. However, STAT6 was not involved in the proliferation of myogenic cells in vitro and in vivo.ConclusionResults suggest that STAT6 functions as an inhibitor of adult myogenesis. Moreover, results suggest that the IL-4-STAT6 signaling axis is unlikely to be responsible for myotube formation.
Highlights
The signal transducer and activator of transcription 6 (STAT6) transcription factor plays a vitally important role in immune cells, where it is activated mainly by interleukin-4 (IL-4)
STAT6 is deactivated during myotube formation, but IL-4 stimulates STAT6 activity We first isolated myoblasts from WT mice and incubated the cells in Differentiation medium (DM) for 24 and 48 h myotube formation to investigate phosphorylated-STAT6 (p-STAT6) (Fig. 1a)
We examined the effects of IL-4 on STAT6 activation
Summary
The signal transducer and activator of transcription 6 (STAT6) transcription factor plays a vitally important role in immune cells, where it is activated mainly by interleukin-4 (IL-4). Because IL-4 is an essential cytokine for myotube formation, STAT6 might be involved in myogenesis as part of IL-4 signaling. The signal transducer and activator of transcription 6 (STAT6) plays a fundamentally important role in immune cells’ cellular function [12, 13]. Its activation prevents apoptotic cell death in B cells [15] It is involved in the fusion of macrophages to generate multinucleated giant cells in response to inflammation [16]. Recent studies have demonstrated the involvement of STAT6 in microglial activation in the brain tissue [17]. The role of STAT6 in peripheral tissues remains unclear
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