Colonic mucin‐2 attenuates acute necrotizing pancreatitis in rats by modulating intestinal homeostasis
Colonic mucin‐2 attenuates acute necrotizing pancreatitis in rats by modulating intestinal homeostasis
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DOI：
10.1096/fj.202201998r
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发表时间：
2023-07
期刊：
影响因子：
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通讯作者：
Zehua Huang;Huimin Wu;Junjie Fan;Qixiang Mei;Yang Fu;Nuoming Yin;Binqiang Xu;S. Luo;
中科院分区：
文献类型：
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作者：
Zehua Huang;Huimin Wu;Junjie Fan;Qixiang Mei;Yang Fu;Nuoming Yin;Binqiang Xu;S. Luo;
杯状细胞分泌的粘蛋白-2（MUC2）参与肠道屏障，但其在急性坏死性胰腺炎（ANP）中的作用机制仍不清楚。在急性胰腺炎（AP）患者中，杯状细胞（MUC2、FCGBP、CLCA1和TFF3）功能下降，且MUC2与AP严重程度呈负相关。与 ANP 大鼠相比，用毛果芸香碱 (PILO)（PILO+ANP 大鼠）消耗 MUC2 的 ANP 大鼠表现出更严重的胰腺和结肠损伤、杯状细胞功能障碍、肠道菌群失调和细菌易位。粪便GC-MS分析显示，PILO+ANP大鼠的丁酸、异丁酸、异戊酸和己酸水平低于ANP大鼠。 MUC2 的表达与结肠损伤和肠道菌群失调相关。 ANP大鼠中补充MUC2可以缓解所有这些现象，并且杯状细胞功能也部分逆转。 TNF-α 处理的类集加剧了杯状细胞功能障碍。 MUC2 表达与促炎细胞因子（IL-1β 和 IL-6）水平呈负相关（p < .05），与紧密连接蛋白（Claudin 1、Occludin 和 ZO1）的表达呈正相关（p < .05）。通过 siRNA 下调 MUC2 会增加结肠中促炎细胞因子的水平。 MUC2 可能维持肠道稳态以缓解 ANP。
Mucin‐2 (MUC2) secreted by goblet cells participates in the intestinal barrier, but its mechanism in acute necrotizing pancreatitis (ANP) remains unclear. In acute pancreatitis (AP) patients, the functions of goblet cells (MUC2, FCGBP, CLCA1, and TFF3) decreased, and MUC2 was negatively correlated with AP severity. ANP rats treated with pilocarpine (PILO) (PILO+ANP rats) to deplete MUC2 showed more serious pancreatic and colonic injuries, goblet cell dysfunction, gut dysbiosis, and bacterial translocation than those of ANP rats. GC‐MS analysis of feces showed that PILO+ANP rats had lower levels of butyric acid, isobutyric acid, isovaleric acid, and hexanoic acid than those of ANP rats. The expression of MUC2 was associated with colonic injury and gut dysbiosis. All these phenomena could be relieved, and goblet cell functions were also partially reversed by MUC2 supplementation in ANP rats. TNF‐α‐treated colonoids had exacerbated goblet cell dysfunction. MUC2 expression was negatively correlated with the levels of pro‐inflammatory cytokines (IL‐1β and IL‐6) (p < .05) and positively related to the expression of tight junction proteins (Claudin 1, Occludin, and ZO1) (p < .05). Downregulating MUC2 by siRNA increased the levels of the pro‐inflammatory cytokines in colonoids. MUC2 might maintain intestinal homeostasis to alleviate ANP.