Primary cilium-mediated signaling cascade suppresses age-related biliary fibrosis

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.

Automated summary

Using cilium-deficient mice, this study found that disruption of ciliary homeostasis in biliary epithelial cells (BECs) in aged mice leads to significant bile duct proliferation, augmented biliary fibrosis, and heightened indicators of liver injury. RNA-sequencing data revealed dysregulation of genes associated with various biological processes. Loss of primary cilia also significantly enhanced signaling pathways driving the development of biliary fibrosis. Overall, this study highlights the importance of the primary cilium as a potential therapeutic target in the treatment of fibrosing cholangiopathies.