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

Abstract

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.

XIAP-mediated degradation of IFT88 disrupts HSC cilia to stimulate HSC activation and liver fibrosis

“…However, no cilia were present on hepatocytes, which comprise about 80% of the cells in the liver (Mansini et al, 2018 ). Bile duct epithelial cells (BECs), also known as cholangiocytes, represent the only cell type in the liver that has been reported to contain cilia, but the absence of cilia on BECs only cause biliary fibrosis in aged mice and does not affect the development of advanced fibrosis or cirrhosis during thioacetamide-induced chronic liver injury (Chen et al, 2022 ; Hong et al, 2023 ; Huang et al, 2006 ). Thus, the role of cilia in liver fibrosis needs further investigation.…”

Dynamic changes of endothelial and stromal cilia are required for the maintenance of corneal homeostasis

“…Primary cilia, hair‐like structures protruding from the surface of almost all mammalian cells, including corneal epithelial and endothelial cells (Allison, 2020; Blitzer et al, 2011; Song & Zhou, 2020; Wu et al, 2023). Functioning as sensory organelles, primary cilia play pivotal roles in cell signaling and tissue homeostasis (Hong et al, 2023; Mill et al, 2023). In the mature mammalian corneal epithelium, primary cilia exist only in the basal layer (Grisanti et al, 2016).…”