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Semin Liver Dis
DOI: 10.1055/a-2563-9791
Review Article

Primary Cilia in Hepatic Biliary Hyperplasia: Implications for Liver Diseases

Kishor Pant   *
1   The Hormel Institute, University of Minnesota, Austin, Minnesota
,
Estanislao Peixoto   *
1   The Hormel Institute, University of Minnesota, Austin, Minnesota
,
Sergio A. Gradilone
1   The Hormel Institute, University of Minnesota, Austin, Minnesota
2   Masonic Cancer Centre, University of Minnesota, Minneapolis, Minnesota
› Author Affiliations
Funding This work was supported by National Institutes of Health Grant R01DK132781 (to S.A.G.), Cholangiocarcinoma Foundation (to K.P.), and The Hormel Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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Abstract

Primary cilia, hair-like projections on the surface of various cell types, play crucial roles in sensing and regulating environmental cues within the liver, particularly among cholangiocytes. These structures detect changes in bile composition, flow, and other biochemical signals, integrating this information to modulate cellular processes. Dysfunction in cholangiocyte cilia—whether due to structural abnormalities or genetic mutations—has been linked to an array of cholangiopathies and ciliopathies. These include conditions such as biliary atresia, cholangiocarcinoma, primary sclerosing cholangitis, and polycystic liver diseases, each with distinct clinical phenotypes influenced by impaired ciliary function. Given the complexity of the ciliary proteome and its role in cellular signaling, including the Hedgehog, Wnt, and TGR5 pathways, ciliary dysfunction disrupts essential signaling cascades, thus driving disease progression. While over 40 gene mutations are associated with ciliopathic features, there may be additional contributors within the expansive ciliary proteome. This study synthesizes current knowledge on cholangiocyte cilia, emphasizing their mechanistic role in liver disease, and highlights emerging therapeutic strategies aimed at restoring ciliary function. In conclusion, ciliotherapies are proposed as a promising approach for addressing cholangiopathies, with the potential to shift the current therapeutic landscape.

Keywords

primary cilia - cholangiocyte - ciliopathy - polycystic liver diseases - primary sclerosing cholangitis - cholangiocarcinoma - ciliotherapies

* Equal contribution.




Publication History

Accepted Manuscript online:
21 March 2025

Article published online:
25 April 2025

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