Septin-7 is indispensable in skeletal muscle regeneration: Calcium Signaling and Excitation–Contraction in Cardiac, Skeletal and Smooth Muscle

Septins are considered as the fourth component of the cytoskeleton, with septin-7 isoform playing a critical role in myogenic cell division and fusion. Skeletal muscle regeneration is a highly orchestrated process that requires many steps, including proper cell division to achieve functional recovery. Here, the role of septin-7 was investigated in this complex process. To this end, muscle injury was induced in wild type BL6/C57 and septin-7–conditional (mer-Cre-mer) knock-down mice by in vivo BaCl₂ injection to the left m. tibialis anterior muscle (TA) of the mice (the right m. tibialis anterior muscle was nontreated control). Mice were sacrificed 4 and 14 d later to reflect the early (monitored by PAX7 level) and late (monitored by myogenin level) phases of muscle regeneration. Western blotting was used to follow the changes of septin-7, PAX7, and myogenin expression at the protein level, while changes of mRNA were detected by qPCR. Morphological differences were visualized by HE staining. Levels of septin-7 protein increased 4 and 14 d after injury in BL6/C57 mice and mRNA expression of SEPT7 showed significant elevation both 4 and 14 d after injection in Cre⁺ mice only, considered to be a compensatory increase of mRNA expression of SEPT7 in order to ensure the appropriate regeneration process. Furthermore, up-regulation of septin-7 protein was more pronounced on day 14 in both Cre⁻ and Cre⁺ mice, which may indicate its importance in the later phase of regeneration. Level of PAX7 and myogenin were also increased 4 and 14 d after injury in BL6/C57, Cre⁻, and Cre⁺ mice, respectively. Taken together, our data suggest the importance of septin-7 in skeletal muscle regeneration.