Upregulation of complement C1q reflects mucosal regeneration in a mouse model of colitis

Med Mol Morphol. 2021 Jun;54(2):87-94. doi: 10.1007/s00795-020-00266-2. Epub 2020 Oct 7.

Abstract

Confirming mucosal healing is important in inflammatory bowel disease treatment. Complement C1q-mediated Wnt signaling activation has recently been suggested to mediate tissue repair and mucosal regeneration. We investigated the involvement of complement C1q and Wnt signaling in intestinal mucosal regeneration using a murine colitis model. The colitis model was established by providing C57BL/6J mice with 4% dextran sodium sulfate (DSS) for 1 week (inflammation phase) followed by regular water for 2 weeks (recovery phase). After 3 weeks, we investigated the relationship between C1q in serum and colonic tissue during the inflammation and recovery phases. We assessed Wnt signaling activity by evaluating β-catenin expression in mouse intestinal tissue. Serum C1q levels were elevated during the recovery phase. C1q-specific staining indicated high C1q expression in pathological intestinal tissue during the inflammation and recovery phases. C1q mRNA and protein expression was increased during both phases. Interestingly, C1q-expressing cells were consistent with macrophages (F4/80-positive cells). Moreover, the expression of β-catenin increased in the colonic tissues during the recovery phase of DSS-induced colitis but decreased during the inflammation phase of DSS-induced colitis. C1q expression may mediate Wnt signaling activity and intestinal epithelial regeneration.

Keywords: C1q; Inflammatory bowel disease; Lgr5; Wnt signaling; β-catenin.

MeSH terms

  • Animals
  • Colitis / genetics
  • Colitis / metabolism*
  • Colitis / physiopathology
  • Complement C1q / genetics*
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • Inflammation
  • Intestinal Mucosa / physiology*
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Regeneration*
  • Up-Regulation
  • Wnt Signaling Pathway*
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • beta Catenin
  • Complement C1q