关键词: TGF-β信号； ,  , 肌损伤； ,  , 巨噬细胞胞葬； ,  , 炎症

Abstract: Objective    To explore the role of skeletal muscle intrinsic transforming growth factor Beta (TGF-β) signaling on macrophages efferocytosis in inflamed muscle induced by Cardiotoxin (CTX ) injection. Methods    Wild C57BL/6 mice (control group) and mice with skeletal muscle-specific deficiency of TGF-βII (SM TGF-βr2-/- group) were selected. Acute injured skeletal muscle was induced by CTX injection to the tibialis anterior muscle. After injection, the differences of the exudation of macrophages, macrophages phenotype, apoptotic cells and the role on macrophages efferocytosis in the inflamed muscle between the two groups were compared. Ultraviolet irradiation was taken to induce of apoptotic cells. In vitro, differentiation culture of primary WT, or SM TGF-βr2-/- myoblasts (MPCs) were co-cultured with macrophages and apoptotic cells to compare and analyze the differences of the role on macrophages efferocytosis.    Results    Compared with the control group, the exudation of inflammatory cells in the injured muscle in SM TGF-βr2-/- group significantly increased, mainly contained mononuclear cells/macrophages. The proportion of M1 macrophages significantly increased (P<0.05), but the proportion of M2 macrophages and the role on macrophages efferocytosis significantly decreased (P<0.05). In the co-cultured system in vitro, compared with the WT-MPCs co-culture system, the role on macrophages efferocytosis and the proportion of M2 macrophages significantly decreased in TGF-βr2-/- -MPCs co-culture system in the pro-inflammatory milieu (P<0.05). Conclusions    Intrinsic TGF-β signaling can promote the role on macrophages efferocytosis in the injured muscle by regulating macrophage phenotype, thus relieving local inflammation and accelerating muscle repair.

Key words:  TGF-β signaling; ,  , Muscle injury; ,  , Macrophages , efferocytosis; ,  , Inflammation