Primary cilium‐mediated signaling cascade suppresses age‐related biliary fibrosis
Primary cilium‐mediated signaling cascade suppresses age‐related biliary fibrosis
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DOI：
10.1002/jcp.31113
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发表时间：
2023-09
影响因子：
5.6
通讯作者：
Renjie Hong;Xiaoyu Tian;Hongbo Ma;Hua Ni;Jia Yang;Weiwen Bu;Te Li;Song Yang;Dengwen Li;Min Liu;Yanjie Tan
中科院分区：
文献类型：
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作者：
Renjie Hong;Xiaoyu Tian;Hongbo Ma;Hua Ni;Jia Yang;Weiwen Bu;Te Li;Song Yang;Dengwen Li;Min Liu;Yanjie Tan
初级纤毛在胆管上皮细胞（BEC）的生理学中越来越被认为是一个关键的角色。然而，初级纤毛在年龄相关性胆道纤维化发展中的确切作用仍不清楚。在本文中，使用纤毛缺陷小鼠，我们证明了老年小鼠BEC中纤毛稳态的破坏导致显著的胆管增殖，增强的胆管纤维化和肝损伤指标的升高。我们的RNA测序数据揭示了与胆汁分泌、脂肪酸代谢和炎症等各种生物学过程相关的基因失调。初级纤毛的丧失也显著增强了驱动胆道纤维化发展的信号通路。我们的研究结果共同表明，老年小鼠BEC中初级纤毛的丧失引发了一系列导致胆道纤维化的信号传导事件，突出了初级纤毛作为治疗纤维化胆管病的潜在治疗靶点。
The primary cilium is increasingly recognized as a crucial player in the physiology of biliary epithelial cells (BECs). However, the precise role of primary cilia in the development of age‐related biliary fibrosis remains unclear. Herein, using cilium‐deficient mice, we demonstrate that disruption of ciliary homeostasis in BECs in aged mice leads to significant bile duct proliferation, augmented biliary fibrosis, and heightened indicators of liver injury. Our RNA‐sequencing data revealed a dysregulation in genes associated with various biological processes such as bile secretion, fatty acid metabolism, and inflammation. Loss of primary cilia also significantly enhanced signaling pathways driving the development of biliary fibrosis. Our findings collectively suggest that loss of primary cilia in the BECs of aged mice initiates a cascade of signaling events that contribute to biliary fibrosis, highlighting the primary cilium as a potential therapeutic target in the treatment of fibrosing cholangiopathies.