State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Cell Ecosystem, College of Life Sciences, Nankai University, Tianjin, China.
Center for Cell Structure and Function, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, China.
J Cell Physiol. 2023 Nov;238(11):2600-2611. doi: 10.1002/jcp.31113. Epub 2023 Sep 8.
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.
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因素。然而，初级纤毛在与年龄相关的胆管纤维化发展中的确切作用仍不清楚。在此，我们使用纤毛缺陷小鼠，证明了在老年小鼠中 BEC 中的纤毛内稳态的破坏导致显著的胆管增殖、增强的胆管纤维化和肝脏损伤的指标升高。我们的 RNA 测序数据揭示了与各种生物学过程相关的基因失调，如胆汁分泌、脂肪酸代谢和炎症。初级纤毛的丧失也显著增强了驱动胆管纤维化发展的信号通路。我们的研究结果表明，老年小鼠的 BEC 中初级纤毛的丧失引发了一系列信号事件，导致胆管纤维化，突出了初级纤毛作为治疗纤维性胆管病的潜在治疗靶点。
