Intestinal stem cells (ISCs) sustain epithelial renewal by dynamically altering behaviors of proliferation and differentiation in response to various nutrition and stress inputs. However, how ISCs integrate bioactive substance morin cues to protect against heat-stable enterotoxin b (STb) produced by Escherichia coli remains an uncertain question with implications for treating bacterial diarrhea. Our recent work showed that oral mulberry leaf-derived morin improved the growth performance in STb-challenged mice. Furthermore, morin supplementation reinstated the impaired small-intestinal epithelial structure and barrier function by stimulating ISC proliferation and differentiation as well as supporting intestinal organoid expansion ex vivo. Importantly, the Wnt/β-catenin pathway, an ISC fate commitment signal, was reactivated by morin to restore the jejunal crypt-villus architecture in response to STb stimulation. Mechanically, the extracellular morin-initiated β-catenin axis is dependent or partially dependent on the Wnt membrane receptor Frizzled7 (FZD7). Our data reveal an unexpected role of leaf-derived morin, which represents molecular signaling targeting the FZD7 platform instrumental for controlling ISC regeneration upon STb injury.

中文翻译：

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桑叶来源的桑色素通过与 Frizzled7 结合激活 β-Catenin，促进热稳定肠毒素 b 损伤时肠干细胞的扩张

肠干细胞（ISC）通过动态改变增殖和分化行为来响应各种营养和应激输入，从而维持上皮细胞更新。然而，ISC 如何整合生物活性物质桑色素线索来防止大肠杆菌产生的热稳定性肠毒素 b (STb)仍然是一个不确定的问题，这对治疗细菌性腹泻有影响。我们最近的研究表明，口服桑叶桑色素可改善 STb 攻击小鼠的生长性能。此外，桑色素补充剂通过刺激 ISC 增殖和分化以及支持离体肠道类器官扩张来恢复受损的小肠上皮结构和屏障功能。重要的是，Wnt/β-连环蛋白途径（ISC 命运承诺信号）被桑色素重新激活，以响应 STb 刺激而恢复空肠隐窝绒毛结构。从机械角度来说，细胞外桑色素启动的 β-连环蛋白轴依赖或部分依赖于 Wnt 膜受体 Frizzled7 (FZD7)。我们的数据揭示了叶源桑色素的意想不到的作用，它代表了针对 FZD7 平台的分子信号传导，有助于控制 STb 损伤后的 ISC 再生。