LKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis.
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Embargo End Date
ICR Authors
Authors
Xu, Z
Davies, ER
Yao, L
Zhou, Y
Li, J
Alzetani, A
Marshall, BG
Hancock, D
Wallis, T
Downward, J
Ewing, RM
Davies, DE
Jones, MG
Wang, Y
Davies, ER
Yao, L
Zhou, Y
Li, J
Alzetani, A
Marshall, BG
Hancock, D
Wallis, T
Downward, J
Ewing, RM
Davies, DE
Jones, MG
Wang, Y
Document Type
Journal Article
Date
2024-05-01
Date Accepted
2023-06-28
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 signalling. 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 downregulation 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 signalling 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.
Citation
Genes and Diseases, 2024, 11 (3), pp. 101065 -
Source Title
Genes and Diseases
Publisher
KEAI PUBLISHING LTD
ISSN
2352-4820
eISSN
2352-3042
2352-3042
2352-3042
Collections
Research Team
Lung Cancer Group