CYLD/HDAC6 signaling regulates the interplay between epithelial-mesenchymal transition and ciliary homeostasis during pulmonary fibrosis

作者：Hua Ni, Miao Chen, Dan Dong, Yunqiang Zhou, Yu Cao, Ruixin Ge, Xiangrui Luo, Yutao Wang, Xifeng Dong, Jun Zhou, Dengwen Li, Songbo Xie, Min Liu · 发表于：Cell Death and Disease · 年份：2024 · DOI：10.1038/s41419-024-06972-4 · 被引用次数：15 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Neonatal Respiratory Health Research、Histiocytic Disorders and Treatments

The primary cilium behaves as a platform for sensing and integrating extracellular cues to control a plethora of cellular activities. However, the functional interaction of this sensory organelle with epithelial-mesenchymal transition (EMT) during pulmonary fibrosis remains unclear. Here, we reveal a critical role for cylindromatosis (CYLD) in reciprocally linking the EMT program and ciliary homeostasis during pulmonary fibrosis. A close correlation between the EMT program and primary cilia is observed in bleomycin-induced pulmonary fibrosis as well as TGF-β-induced EMT model. Mechanistic study reveals that downregulation of CYLD underlies the crosstalk between EMT and ciliary homeostasis by inactivating histone deacetylase 6 (HDAC6) during pulmonary fibrosis. Moreover, manipulation of primary cilia is an effective means to modulate the EMT program. Collectively, these results identify a pivotal role for the CYLD/HDAC6 signaling in regulating the reciprocal interplay between the EMT program and ciliary homeostasis during pulmonary fibrosis.