LKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis.
Date
2024-05-01ICR Author
Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Genetics & Heredity
LKB1
CAB39L
EMT
Crosstalk
Pulmonary fibrosis
IDIOPATHIC PULMONARY-FIBROSIS
SIGNALING PATHWAY
AUTOPHAGY
KINASE
CANCER
Research team
Lung Cancer Group
Language
eng
Date accepted
2023-06-28
License start date
2024-05-01
Citation
Genes and Diseases, 2024, 11 (3), pp. 101065 -
Publisher
KEAI PUBLISHING LTD