Increased Primary Cilia in Idiopathic Pulmonary Fibrosis

  • Lee, Junguee (Department of Pathology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Oh, Dong Hyun (Department of Radiology, Konyang University Hospital) ;
  • Park, Ki Cheol (Clinical Research Institute, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Choi, Ji Eun (Department of Pathology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Kwon, Jong Beom (Department of Thoracic and Cardiovascular Surgery, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Lee, Jongho (Department of Thoracic and Cardiovascular Surgery, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Park, Kuhn (Department of Thoracic and Cardiovascular Surgery, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Sul, Hae Joung (Department of Pathology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
  • Received : 2017.11.21
  • Accepted : 2017.12.05
  • Published : 2018.03.31


Primary cilia are solitary, non-motile, axonemal microtubule-based antenna-like organelles that project from the plasma membrane of most mammalian cells and are implicated in transducing hedgehog signals during development. It was recently proposed that aberrant SHH signaling may be implicated in the progression of idiopathic pulmonary fibrosis (IPF). However, the distribution and role of primary cilia in IPF remains unclear. Here, we clearly observed the primary cilia in alveolar epithelial cells, fibroblasts, and endothelial cells of human normal lung tissue. Then, we investigated the distribution of primary cilia in human IPF tissue samples using immunofluorescence. Tissues from six IPF cases showed an increase in the number of primary cilia in alveolar cells and fibroblasts. In addition, we observed an increase in ciliogenesis related genes such as IFT20 and IFT88 in IPF. Since major components of the SHH signaling pathway are known to be localized in primary cilia, we quantified the mRNA expression of the SHH signaling components using qRT-PCR in both IPF and control lung. mRNA levels of SHH, the coreceptor SMO, and the transcription factors GLI1 and GLI2 were upregulated in IPF compared with control. Furthermore, the nuclear localization of GLI1 was observed mainly in alveolar epithelia and fibroblasts. In addition, we showed that defective KIF3A-mediated ciliary loss in human type II alveolar epithelial cell lines leads to disruption of SHH signaling. These results indicate that a significant increase in the number of primary cilia in IPF contributes to the upregulation of SHH signals.


Supported by : National Research Foundation of Korea (NRF), Catholic Medical Center


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