复旦大学罗凌飞和赵天宇团队的最新研究揭示，胆囊源性维甲酸信号驱动受损肝内胆管的重建。相关论文于2025年1月8日发表在《自然—细胞生物学》杂志上。

研究人员表示，肝内胆管（IHBD）网络的严重损害发生在多种人类晚期胆管疾病中，如原发性硬化性胆管炎、胆道闭锁和终末期原发性胆管炎。严重受损的肝内胆管网络能否以及如何重建仍不清楚。

本研究表明，尽管胆囊与肝内胆管（IHBD）没有直接连接，但它们之间存在共同的肝总管（CHD）。严重损伤肝内胆管网络会诱导胆囊平滑肌细胞（SMCs），迁移至肝总管并覆盖其表面，在小鼠和斑马鱼模型中均有观察到。

这些来源于胆囊，覆盖肝总管的胆囊平滑肌细胞产生视黄酸，激活肝总管中的Sox9b，从而驱动肝总管细胞的增殖和向内肝脏的生长，重建肝内胆管网络。

本研究揭示了胆囊在受损肝脏恢复中的，一个迄今未被认识的功能，并阐明了胆囊与肝脏通过器官间细胞迁移相互沟通，以促进组织再生的机制。因此，进行胆囊切除术将会导致肝脏健康，出现先前未曾预料到的损害。

附：英文原文

Title: Gallbladder-derived retinoic acid signalling drives reconstruction of the damaged intrahepatic biliary ducts

Author: He, Jianbo, Li, Shuang, Yang, Zhuolin, Ma, Jianlong, Qian, Chuanfang, Huang, Zhuofu, Li, Linke, Yang, Yun, Chen, Jingying, Sun, Yunfan, Zhao, Tianyu, Luo, Lingfei

Issue&Volume: 2025-01-08

Abstract: Severe damage to the intrahepatic biliary duct (IHBD) network occurs in multiple human advanced cholangiopathies, such as primary sclerosing cholangitis, biliary atresia and end-stage primary biliary cholangitis. Whether and how a severely damaged IHBD network could reconstruct has remained unclear. Here we show that, although the gallbladder is not directly connected to the IHBD, there is a common hepatic duct (CHD) in between, and severe damage to the IHBD network induces migration of gallbladder smooth muscle cells (SMCs) to coat the CHD in mouse and zebrafish models. These gallbladder-derived, CHD-coating SMCs produce retinoic acid to activate Sox9b in the CHD, which drives proliferation and ingrowth of CHD cells into the inner liver to reconstruct the IHBD network. This study reveals a hitherto unappreciated function of the gallbladder in the recovery of injured liver, and characterizes mechanisms involved in how the gallbladder and liver communicate through inter-organ cell migration to drive tissue regeneration. Carrying out cholecystectomy will thus cause previously unexpected impairments to liver health.

DOI: 10.1038/s41556-024-01568-8

Source: https://www.nature.com/articles/s41556-024-01568-8