时间标签：数据日期 2026-11-05 · 生成时间 2026-11-05 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/11/02 – 2026/11/06 ｜ 情报发生日期 2026-11-05
研究问题
Herein, we investigated the role of CASM utilizing genetic manipulation of the key CASM regulator Rubicon, to evaluate the role of CASM in shaping intestinal barrier integrity and host-protection in response to S.t infection.In brief, our results revealed that Rubicon is essential for maintaining intestinal barrier integrity by playing a critical role in regulating intestinal epithelial architecture, leading to maintenance of gut microbial homeostasis.；We hypothesized that the Rubcn-/- ileum would have a reduction in Paneth cell number and lysozyme expression consistent with ATG16L1-deficient mice when compared to WT ileums.；We then broadened our scope to determine whether there was a change in the overall length of the Rubcn-/- intestines (Figure 1D).
方法
In addition to CASM regulating immune homeostasis, we further hypothesized that Rubicon and CASM could play a role in maintaining intestinal anatomical and microbial homeostasis via regulation of intestinal permeability as recently suggested (46).；Herein, we investigated the role of CASM utilizing genetic manipulation of the key CASM regulator Rubicon, to evaluate the role of CASM in shaping intestinal barrier integrity and host-protection in response to S.t infection.In brief, our results revealed that Rubicon is essential for maintaining intestinal barrier integrity by playing a critical role in regulating intestinal epithelial architecture, leading to maintenance of gut microbial homeostasis.；Cumulatively, this work identifies a novel role for Rubicon in maintaining intestinal villi architecture including junctional protein homeostasis, microbial homeostasis within the gut, and protection against enteric infections including S.t septicemia.2Materials & methods2.1MiceThe Rubcn knockout (Rubcn-/-) mice were previously established (49).
核心结论
These data suggest that CASM-deficiency increases gut permeability and support the hypothesis that CASM is critical for maintaining gut integrity.Figure 1Rubicon is essential for maintaining paracellular integrity.；Taken together these data suggest that in addition to restricting gut permeabilization, CASM is influencing the anatomical organization of both small and large intestine.3.2Rubicon-deficiency leads to altered epithelial junctional organizationGiven the increased intestinal permeability observed in the Rubcn-/- mice, we next investigated whether Rubicon-deficiency affected the organization of key epithelial junctional proteins.；These findings were further supported by biochemical fractionation demonstrating clear increases in cytosolic E-cadherin in the Rubcn-/- mice compared to their WT counterparts which had an approximate 4x increase in E-cadherin found in the membrane fraction compared to the cytosol (Figures 2C, D).Figure 2Rubicon-deficiency leads to altered epithelial junctional organization.
局限
However, proliferation of lymphoid cells was not as marked as observed in the small intestine (Supplementary Figure S3K).；However, the cleaved caspase-3 analysis demonstrated only a nonsignificant increasing trend when normalized to total caspase-3.；They do not, however, establish whether microbiome alterations initiate the barrier phenotype or arise as its consequence.
对本项目的价值
中高价值：属「营养感知—自噬—蛋白稳态轴」方向；mTOR / 自噬 / 蛋白质稳态栏目可用作本项目文献库与综述素材。 ｜ 价值分 3.0/5（★★★☆☆）
全文来源
PubMed PMC JATS（正文 60,215 字符，题名指纹 1.0，已过 PubMed PMCID 官方关联 + 题名指纹 + 正文长度归属校验）
原文题录
- 中文题名：Rubicon 是免疫屏障完整性的关键调控者并限制肠道病原感染
- 英文标题：Rubicon is a critical regulator of immune barrier integrity and limits enteric pathogen infection.
- 期刊与标识：Frontiers in immunology · PMID 42973669 · DOI 10.3389/fimmu.2026.1889997 · PMC PMC13724405