美国国立卫生研究院Chuan Wu小组发现，肠道-肝脏轴校准肠道干细胞的适应性。这一研究成果于2024年1月26日在线发表在国际学术期刊《细胞》上。

通过肝切除术以及转录组和蛋白质组分析，研究人员发现了肝源性可溶性Wnt抑制因子——色素上皮衍生因子（PEDF），它通过抑制Wnt/β-catenin信号通路，抑制肠干细胞（ISC）过度增殖以维持肠道稳态。此外，研究人员发现肠道炎症产生的微生物危险信号可被肝脏感知，从而通过过氧化物酶体增殖激活受体-α（PPARα）抑制PEDF的产生。这种抑制释放了ISC的增殖，从而加速了肠道组织的修复。

此外，用非诺贝特（一种临床上用于治疗低血脂症的PPARα激动剂）治疗小鼠会因PEDF的活性而提高小鼠对结肠炎的易感性。因此，研究人员确定了PEDF在通过肠道和肝脏之间的相互影响校准肠道稳态的ISC扩张方面的独特作用。

据悉，人们认识到，肠道和肝脏通过胆道、门静脉和全身循环相互沟通。然而，这种肠道-肝脏轴如何调节肠道生理仍不清楚。

附：英文原文

Title: Gut-liver axis calibrates intestinal stem cell fitness

Author: Girak Kim, Zuojia Chen, Jian Li, Jialie Luo, Felipe Castro-Martinez, Jan Wisniewski, Kairong Cui, Yan Wang, Jialei Sun, Xiaobai Ren, Susan E. Crawford, S. Patricia Becerra, Jimin Zhu, Taotao Liu, Sui Wang, Keji Zhao, Chuan Wu

Issue&Volume: 2024-01-26

Abstract: The gut and liver are recognized to mutually communicate through the biliary tract,portal vein, and systemic circulation. However, it remains unclear how this gut-liveraxis regulates intestinal physiology. Through hepatectomy and transcriptomic and proteomicprofiling, we identified pigment epithelium-derived factor (PEDF), a liver-derivedsoluble Wnt inhibitor, which restrains intestinal stem cell (ISC) hyperproliferationto maintain gut homeostasis by suppressing the Wnt/β-catenin signaling pathway. Furthermore,we found that microbial danger signals resulting from intestinal inflammation canbe sensed by the liver, leading to the repression of PEDF production through peroxisomeproliferator-activated receptor-α (PPARα). This repression liberates ISC proliferationto accelerate tissue repair in the gut. Additionally, treating mice with fenofibrate,a clinical PPARα agonist used for hypolipidemia, enhances colitis susceptibility dueto PEDF activity. Therefore, we have identified a distinct role for PEDF in calibratingISC expansion for intestinal homeostasis through reciprocal interactions between thegut and liver.

DOI: 10.1016/j.cell.2024.01.001

Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00003-5