Effects of autoimmune abnormalities on skeletal muscle regeneration after needle puncture in mice

Exp Biol Med (Maywood). 2023 Oct;248(20):1829-1840. doi: 10.1177/15353702231198073. Epub 2023 Sep 26.

Abstract

Regeneration of injured skeletal muscles is supported by the activation of satellite cells, and excessive traumatic injuries may trigger abnormal processes, such as fibrosis. Because the participation of immune cells is crucial during skeletal muscle repair, systemic autoimmune diseases impair their regeneration. This study focused on a traumatic injury by injection and investigated the effect of autoimmune diseases on skeletal muscle regeneration. Male mice of MRL/MpJ-Faslpr/lpr and MRL/MpJ (6-7 months old) were used for autoimmune disease and healthy groups. The abdominal walls punctured by a needle were histologically analyzed at 1, 3, and 8 days postinjection. In both groups, injured skeletal muscle tissues showed necrosis and inflammatory cell infiltrations on day 1, increased cell density at 3 days, and regenerative myotubes with central nuclei without fibrosis at 8 days. Gr-1+ neutrophils at injured skeletal muscle were abundant at 1 day, and then substantially decreased starting from 3 days in both groups. The number of CD3+ T cells was remarkably higher in MRL/MpJ-Faslpr/lpr than that in MRL/MpJ at 1 day, and a similar tendency was observed in B220+ B cells. The numbers of IBA1+ macrophages and bromodeoxyuridine-incorporating cells tended to be higher at 3 days, and those of the latter, mainly proliferating paired-box-7+ satellite cells, showed significance at other time points and negatively correlated with the autoimmune disease indices, such as spleen weights or serum autoantibody level. Thus, this result suggested that injured skeletal muscle by minor trauma is normally regenerated regardless of the effects of autoimmune diseases, although lymphocyte infiltrations during these processes were more severe in MRL/MpJ-Faslpr/lpr.

Keywords: Autoimmune disease; MRL/MpJ-Faslpr/lpr; histopathology; injection; muscle regeneration; skeletal muscle.

MeSH terms

  • Animals
  • Autoimmune Diseases* / pathology
  • Fibrosis
  • Male
  • Mice
  • Muscle, Skeletal
  • Neutrophils
  • Punctures