| First Author | Zhang C | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 3 | Pages | 1489-99 |
| PubMed ID | 23184935 | Mgi Jnum | J:193878 |
| Mgi Id | MGI:5469808 | Doi | 10.1074/jbc.M112.419788 |
| Citation | Zhang C, et al. (2013) Interleukin-6/signal transducer and activator of transcription 3 (STAT3) pathway is essential for macrophage infiltration and myoblast proliferation during muscle regeneration. J Biol Chem 288(3):1489-99 |
| abstractText | Inflammation and microenvironment play a crucial role in muscle regeneration. IL (interleukin)-6, as a multifunctional cytokine is involved in the processes. However, the causative effect of IL-6 in muscle regeneration remains unclear. In a mouse model of cardiotoxin-induced muscle injury/regeneration, infiltrated monocytes/macrophages produce a high level of IL-6 started on 1 day (24 h) after injury. In IL-6 knock-out (-/-) mice, the muscle regeneration procedure was impaired along with decreased myogenic determination factor (MyoD) and myogenin mRNA level and increased interstitial fibrosis. The IL-6(-/-) mice exhibited less macrophage infiltration, lower inflammatory cytokine (IL-1beta, inducible NO synthase, Transforming growth factor (TGF)-beta1, and IL-10) and chemokine (CCL2, CCL3, and CCL5) expression, and inhibited myoblast proliferation. In vitro, IL-6 deficiency or Signal Transducer and Activator of Transcription 3 (STAT3) knockdown in activated macrophage attenuated the expression of CCL2, CCL3, but not CCL5, which resulted in less macrophage migration. Moreover, inflammatory macrophages promoted myoblast proliferation in an IL-6-dependent manner. Finally, adoptive transfer IL-6(+/+) BM cells into IL-6(-/-) mice rescued the impaired regeneration with improved MyoD and myogenin expression. Taken together, IL-6 expression and the activated STAT3 signaling pathway in monocytes/macrophages is a critical mediator of macrophage migration and myoblast proliferation during muscle regeneration. |
