LKB1 depletion-mediated epithelial–mesenchymal transition induces fibroblast activation in lung fibrosis

Zijian Xu; Elizabeth R. Davies; Liudi Yao; Yilu Zhou; Juanjuan Li; Aiman Alzetani; Ben G. Marshall; David Hancock; Tim Wallis; Julian Downward; Rob M. Ewing; Donna E. Davies; Mark G. Jones; Yihua Wang

doi:10.1016/j.gendis.2023.06.034

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LKB1 depletion-mediated epithelial–mesenchymal transition induces fibroblast activation in lung fibrosis

Full-length article | 更新时间：2024-02-04

- LKB1 depletion-mediated epithelial–mesenchymal transition induces fibroblast activation in lung fibrosis
- Genes & Diseases Vol. 11, Issue 3, (2024)
- 作者机构：
  
  1. University Hospital Southampton,Southampton,UK,SO16 6YD
  2. Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton,Southampton,UK,SO17 1BJ
  3. Oncogene Biology, The Francis Crick Institute,London,UK,NW1 1AT
  4. Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton,Southampton,UK,SO16 6YD
  5. NIHR Southampton Biomedical Research Centre, University Hospital Southampton,Southampton,UK,SO16 6YD
  6. Institute for Life Sciences, University of Southampton,Southampton,UK,SO17 1BJ
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2023.06.034
  CLC：
- Published：2024，
  
  Published Online：1 May 2024，
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Zijian Xu, Elizabeth R. Davies, Liudi Yao, et al. LKB1 depletion-mediated epithelial–mesenchymal transition induces fibroblast activation in lung fibrosis. [J]. Genes & Diseases 11(3).(2024)
DOI：

Zijian Xu, Elizabeth R. Davies, Liudi Yao, et al. LKB1 depletion-mediated epithelial–mesenchymal transition induces fibroblast activation in lung fibrosis. [J]. Genes & Diseases 11(3).(2024) DOI： 10.1016/j.gendis.2023.06.034.

摘要

Abstract

The factors that determine fibrosis progression or normal tissue repair are largely unknown. We previously demonstrated that autophagy inhibition-mediated epithelial–mesenchymal transition (EMT) in human alveolar epithelial type II (ATII) cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine signaling. Here

we report that liver kinase B1 (LKB1) inactivation in ATII cells inhibits autophagy and induces EMT as a consequence. In IPF lungs

this is caused by the down-regulation of

CAB39L

a key subunit within the LKB1 complex. 3D co-cultures of ATII cells and MRC5 lung fibroblasts coupled with RNA sequencing (RNA-seq) confirmed that paracrine signaling between LKB1-depleted ATII cells and fibroblasts augmented myofibroblast differentiation. Together

these data suggest that reduced autophagy caused by LKB1 inhibition can induce EMT in ATII cells and contribute to fibrosis via aberrant epithelial–fibroblast crosstalk.

关键词

Keywords

LKB1CAB39LEMTCrosstalkPulmonary fibrosis

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