Recombinant soluble thrombomodulin accelerates epithelial stem cell proliferation in mouse intestinal organoids and promotes the mucosal healing in colitis
Recombinant soluble thrombomodulin accelerates epithelial stem cell proliferation in mouse intestinal organoids and promotes the mucosal healing in colitis
复制标题
重组可溶性血栓调节蛋白加速小鼠肠道类器官上皮干细胞增殖并促进结肠炎粘膜愈合
DOI：
10.1111/jgh.15656
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Shimaoka M.
中科院分区：
文献类型：
--
作者：
Gaowa A;Park EJ;Kawamoto E;Qin Y;Shimaoka M.
背景与目的上皮再生是炎症性肠病黏膜愈合的关键步骤，受干细胞的密切调控。因此，鉴定诱导干细胞增殖的特异性因子可能有助于开发治疗炎症性肠病的有效策略。重组可溶性血栓调节蛋白（rsTM）以前已被证明可以促进细胞增殖的皮肤和角膜伤口愈合的小鼠models，但其对肠上皮细胞增殖的影响仍不清楚。MethodsMouse肠类器官和葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型被用来评估rsTM对肠上皮细胞增殖的影响。通过共聚焦显微镜研究了类器官的大小和萌芽形态。通过定量真实的时间聚合酶链反应和免疫荧光分析来分析基因表达水平。通过评估体重变化，结肠长度，组织学评分和存活率rsTM对DSS诱导的结肠炎的影响进行了研究。ResultsTM显着刺激肠道类器官的生长，从而增加了表面积和出芽表型的类器官。rsTM还以剂量依赖性方式显著上调肠干细胞特异性和上皮细胞特异性标志物的基因表达。此外，高浓度rsTM治疗显著改善了结肠炎小鼠的体重恢复、组织学结局、结肠长度缩短，并延长了其生存期。结论rsTM促进了肠道类器官中肠干细胞的增殖，并增强了DSS诱导的结肠炎恢复期的粘膜愈合。
Background and AimEpithelial regeneration, a critical step for the mucosal healing in inflammatory bowel disease, is tightly regulated by stem cells. Therefore, identification of the specific factors that induce stem cell proliferation could contribute to the development of effective strategies for treating inflammatory bowel disease. Recombinant soluble thrombomodulin (rsTM) has previously been shown to promote cell proliferation in skin and corneal wound healing in murine models, but its effects on intestinal epithelial cell proliferation remains unclear.MethodsMouse intestinal organoids and dextran sulfate sodium (DSS)‐induced colitis mouse model were used to assess the effects of rsTM on proliferation of intestinal epithelial cells. The size and budding morphologies of organoids were studied by confocal microscopy. The gene expression levels were analyzed by quantitative real‐time polymerase chain reaction and immunofluorescence analysis. The effects of rsTM on DSS‐induced colitis were investigated by evaluating body weight changes, colon length, histological score, and survival rate.ResultsThe rsTM markedly stimulated the growth of intestinal organoids, thereby increasing the surface areas and budding phenotypes of the organoids. rsTM also significantly upregulated the gene expression of intestinal stem cell‐specific and epithelial cell‐specific markers in a dose‐dependent manner. Furthermore, the treatment with high concentrations of rsTM significantly improved the recovery of body weight, histological outcomes, colon length shortening, and prolonged the survival of mice with colitis.ConclusionsThe rsTM promotes intestinal stem cell proliferation in intestinal organoids and enhances the mucosal healing during recovery phase in DSS‐induced colitis.
影响因子：
15.9
作者：
Sugimoto, Ken;Ogawa, Atsuhiro;Mizoguchi, Atsushi
通讯作者：
Mizoguchi, Atsushi
在发炎的肠道组织和上皮细胞中，白介素22信号传导增加了H19长的非编码RNA的表达，从而促进粘膜再生。
影响因子：
29.4
作者：
Geng H;Bu HF;Liu F;Wu L;Pfeifer K;Chou PM;Wang X;Sun J;Lu L;Pandey A;Bartolomei MS;De Plaen IG;Wang P;Yu J;Qian J;Tan XD
通讯作者：
Tan XD
硫糖铝通过 NF-κB 通路阻止过氧化氢延迟肠上皮细胞伤口修复
影响因子：
6.3
作者：
K. Shindo;M. Iizuka;K. Sasaki;S. Konno;H. Itou;Y. Horie;Sumio Watanabe
通讯作者：
Sumio Watanabe