New research demonstrates that the gut–liver axis plays a part in calibrating intestinal stem cell (ISC) expansion during intestinal homeostasis in mice, with a key role for the hepatokine pigment epithelium-derived factor (PEDF).

In a series of experiments using transcriptomics, proteomics and hepatectomy in mouse models, the researchers identified PEDF, a liver-derived soluble WNT inhibitor, which restrained ISC proliferation, maintaining intestinal homeostasis by suppressing the WNT–β-catenin signalling pathway (via LRP5/6). Moreover, the gut–liver axis was involved in PEDF production. Microbial danger signals (lipopolysaccharide) could be sensed by the liver, inhibiting the production of PEDF via liver-derived peroxisome proliferator-activator receptor-α (PPARα). This step allowed ISC proliferation to accelerate tissue repair in the gut after damage to the intestinal epithelium due to colitis. Crucially, treatment of mice with fibrofenate (a PPARα agonist) increased susceptibility to colitis in mouse models via PEDF.

新的研究表明，肠-肝轴在小鼠肠道稳态过程中调节肠干细胞（ISC）扩张中发挥着一定作用，其中肝因子色素上皮衍生因子（PEDF）发挥着关键作用。

在小鼠模型中使用转录组学、蛋白质组学和肝切除术进行的一系列实验中，研究人员发现了 PEDF，一种肝源性可溶性 WNT 抑制剂，它可以抑制 ISC 增殖，通过抑制 WNT-β-连环蛋白信号通路（通过 LRP5/ 6).此外，肠-肝轴参与 PEDF 的产生。肝脏可以感知微生物危险信号（脂多糖），通过肝源性过氧化物酶体增殖物激活受体-α（PPARα）抑制 PEDF 的产生。这一步骤使得 ISC 增殖能够加速肠道上皮因结肠炎而受损后的组织修复。至关重要的是，在小鼠模型中，用 filofenate（一种 PPARα 激动剂）治疗小鼠会通过 PEDF 增加对结肠炎的易感性。