Department of Gastroenterology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan.
Med Mol Morphol. 2021 Jun;54(2):87-94. doi: 10.1007/s00795-020-00266-2. Epub 2020 Oct 7.
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.
在炎症性肠病的治疗中,确认黏膜愈合是很重要的。最近有研究表明,补体 C1q 介导的 Wnt 信号激活可介导组织修复和黏膜再生。我们使用小鼠结肠炎模型研究了补体 C1q 和 Wnt 信号在肠道黏膜再生中的作用。该结肠炎模型通过向 C57BL/6J 小鼠提供 4%的葡聚糖硫酸钠(DSS)1 周(炎症期),然后用普通水 2 周(恢复期)来建立。3 周后,我们研究了血清和结肠组织中的 C1q 在炎症和恢复期之间的关系。通过评估小鼠肠道组织中β-连环蛋白的表达来评估 Wnt 信号活性。在恢复期,血清 C1q 水平升高。C1q 特异性染色表明在炎症和恢复期,病理性肠道组织中 C1q 表达较高。在两个阶段,C1q mRNA 和蛋白表达均增加。有趣的是,表达 C1q 的细胞与巨噬细胞(F4/80 阳性细胞)一致。此外,在 DSS 诱导的结肠炎恢复期,β-连环蛋白在结肠组织中的表达增加,而在 DSS 诱导的结肠炎炎症期,β-连环蛋白的表达减少。C1q 表达可能介导 Wnt 信号活性和肠道上皮再生。