Autophagy is involved in the sclerotic phase of systemic sclerosis

Fukushima J Med Sci. 2020 Apr 22;66(1):17-24. doi: 10.5387/fms.2019-28. Epub 2020 Apr 10.

Abstract

Autophagy is an essential intracellular self-degradation system, and is known to maintain the homeostatic balance between the synthesis, degradation, and recycling of cellular proteins and organelles. Recent studies have suggested a possible role of autophagy in systemic sclerosis (SSc);however, differences in autophagy among pathological phases of SSc have not yet been examined. Therefore, in the current study we investigated the expression pattern of an autophagosome marker protein, microtubule-associated protein 1 light chain 3 (LC3) in the lesional skin of a murine model and human SSc. In bleomycin-induced mouse scleroderma skin, the number of LC3-positive puncta was significantly higher than that in phosphate buffered salts-injected control skin after 4 weeks of treatment. Such an increase, however, was not observed in the skin after 2 weeks of bleomycin treatment, in which few myofibroblasts were detected. In the sclerotic phase of SSc patients, the number of LC3-positive puncta in the lower dermis was significantly higher than in the upper dermis. It was also significantly higher than in the lower dermis of the control patients. No increase in LC3-positive puncta was observed in the skin from SSc patients in edematous phase, in which myofibroblasts were hardly detected. These results suggest that changes in the autophagic degradation system reflect a skin remodeling process that leads to fibrosis.

Keywords: LC3; bleomycin; lysosome; murine model; scleroderma.

MeSH terms

  • Aged
  • Animals
  • Autophagy / physiology*
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / analysis
  • Middle Aged
  • Scleroderma, Systemic / metabolism
  • Scleroderma, Systemic / pathology*
  • Sclerosis
  • Skin / chemistry

Substances

  • MAP1LC3A protein, human
  • Map1lc3b protein, mouse
  • Microtubule-Associated Proteins