CYLD/HDAC6信号调节肺纤维化过程中上皮-间质转化和纤毛稳态之间的相互作用。

IF 8.1 1区 生物学 Q1 CELL BIOLOGY
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
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引用次数: 0

摘要

初级纤毛是感知和整合细胞外线索的平台,可控制大量细胞活动。然而,在肺纤维化过程中,这种感觉细胞器与上皮-间质转化(EMT)之间的功能性相互作用仍不清楚。在这里,我们揭示了肺纤维化过程中圆柱状绒毛膜变性(CYLD)在上皮-间质转化(EMT)程序和纤毛稳态之间相互联系中的关键作用。在博莱霉素诱导的肺纤维化和TGF-β诱导的EMT模型中,我们观察到了EMT程序和初级纤毛之间的密切联系。机理研究发现,在肺纤维化过程中,CYLD的下调通过使组蛋白去乙酰化酶6(HDAC6)失活,成为EMT与纤毛平衡之间相互影响的基础。此外,操纵原发性纤毛是调节 EMT 程序的有效手段。总之,这些结果确定了CYLD/HDAC6信号在肺纤维化过程中调控EMT程序和纤毛稳态之间相互影响的关键作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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

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.

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来源期刊
Cell Death & Disease
Cell Death & Disease CELL BIOLOGY-
CiteScore
15.10
自引率
2.20%
发文量
935
审稿时长
2 months
期刊介绍: Brought to readers by the editorial team of Cell Death & Differentiation, Cell Death & Disease is an online peer-reviewed journal specializing in translational cell death research. It covers a wide range of topics in experimental and internal medicine, including cancer, immunity, neuroscience, and now cancer metabolism. Cell Death & Disease seeks to encompass the breadth of translational implications of cell death, and topics of particular concentration will include, but are not limited to, the following: Experimental medicine Cancer Immunity Internal medicine Neuroscience Cancer metabolism
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