Abstract: Objective   To explore the effects of CaMKIV signaling on muscle inflammatory response and muscle repair post-injury.    Methods    CaMKIV gene deletion (CaMKIV-/-) mice were constructed by using CRISPR/Cas9 technology and identified by PCR. Cardiotoxin (CTX) induced skeletal muscle injury was performed in wild B6 and CaMKIV-/- mice. HE staining was used to observe the inflammation and repair in injured muscles. Dystrophy immunofluorescence staining was used to identify the regenerating myofibers while F4/80 staining to present infiltrated macrophage in inflamed muscle. F4/80, Ly-6C, CD206, Ki67 staining and flow cytometry skill were used to analyze the number and proportion of M1 (F4/80+Ly6C+) and M2 ((F4/80+CD206+) macrophages in the injured muscle, as well proliferation capacity of macrophages (F4/80+Ki67+).    Results   CaMKIV-/- mice were successfully constructed and bred. HE and fluorescence staining showed that, the absence of CaMKⅣ signaling in mice resulted in increasing intramuscular inflammation and delaying muscle repair. The number of the regenerating central nuclear muscle fibers（Dystrophin+） in CaMKⅣ-/- mice was lower than that in WT mice. The number of macrophages (F4/80+) in inflamed muscle from CaMKⅣ-/- mice was significantly higher than that of WT mice, which was dominant by M1 cells, comparing with that of WT mice. In inflamed muscle of CaMKⅣ-/- mice, the number and proportion of proliferating macrophages (F4/80+Ki67+) was significantly higher than that of control mice, but the proliferating macrophages were mainly M1 cells (Ly6C+Ki67+).    Conclusions    The loss of CaMKⅣ signaling leads to the aggravation of muscle inflammation, promotes the exudation and proliferation of M1 macrophages in inflamed muscle, and delays muscle repair after injury.

Key words: Muscle injury,  ,  , CaMKⅣ,  ,  , Macrophage,  ,  , Inflammation,  ,  , Proliferation