Abstract
Repair and regeneration of the injured skeletal myofiber involves fusion of intracellular vesicles with sarcolemma and fusion of the muscle progenitor cells respectively. In vitro experiments have identified involvement of Annexin A1 (Anx A1) in both these fusion processes. To determine if Anx A1 contributes to these processes during muscle repair in vivo, we have assessed muscle growth and repair in Anx A1-deficient mouse (AnxA1−/−). We found that the lack of Anx A1 does not affect the muscle size and repair of myofibers following focal sarcolemmal injury and lengthening contraction injury. However, the lack of Anx A1 delayed muscle regeneration after notexin-induced injury. This delay in muscle regeneration was not caused by a slowdown in proliferation and differentiation of satellite cells. Instead, lack of Anx A1 lowered the proportion of differentiating myoblasts that managed to fuse with the injured myofibers by days 5 and 7 after notexin injury as compared to the wild type (w.t.) mice. Despite this early slowdown in fusion of Anx A1−/− myoblasts, regeneration caught up at later times post injury. These results establish in vivo role of Anx A1 in cell fusion required for myofiber regeneration and not in intracellular vesicle fusion needed for repair of myofiber sarcolemma.
Highlights
Healing injured muscle involves relatively fast repair of the injured myofiber cell membrane by fusion of intracellular membrane with the cell membrane[1]
Similar to what was previously reported[23], we found that body weight of Annexin A1 (Anx A1)− /− mice was indistinguishable from that of w.t. mice, and observed no difference in the weight of the specific muscles including heart, Soleus, EDL, Tibialis Anterior (TA) and Gastrocnemius (Fig. 1)
Our results indicate that Anx A1 deficiency does not inhibit muscle growth, cause muscle damage or decrease the ability of injured myofiber to repair
Summary
Healing injured muscle involves relatively fast (minutes) repair of the injured myofiber cell membrane by fusion of intracellular membrane with the cell membrane[1]. Similar to our observation in vitro that fusion between Anx A1− /− myoblasts is slower at earlier times but catches up[6], we find that the lack of Anx A1 resulted in a significant delay in the muscle regeneration after notexin-induced injury in vivo. This delay in muscle regeneration in Anx A1− /− animals was not associated with deficits in post-injury activation and myogenic differentiation of satellite cells, but with a delay in fusion of activated myoblasts with the regenerating myofibers. Our results substantiate the hypothesis that Anx A1 is involved in cell-cell fusion during myofiber regeneration following acute muscle injury in vivo but not in muscle development or repair of injured myofiber sarcolemma
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