Imperial College London
Alternate

ProfessorFanChung

Faculty of Medicine, National Heart & Lung Institute

Professor of Respiratory Medicine
 
 
 
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Contact

 

+44 (0)20 7594 7954f.chung Website

 
 
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Assistant

 

Miss Carolyn Green +44 (0)20 7594 7959

 
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Location

 

227BGuy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Chen:2023:10.1186/s10020-023-00760-0,
author = {Chen, X-Y and Kao, C and Peng, S-W and Chang, J-H and Lee, Y-L and Laiman, V and Chung, KF and Bhavsar, PK and Heriyanto, DS and Chuang, K-J and Chuang, H-C},
doi = {10.1186/s10020-023-00760-0},
journal = {Mol Med},
title = {Role of DCLK1/Hippo pathway in type II alveolar epithelial cells differentiation in acute respiratory distress syndrome.},
url = {http://dx.doi.org/10.1186/s10020-023-00760-0},
volume = {29},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Delay in type II alveolar epithelial cell (AECII) regeneration has been linked to higher mortality in patients with acute respiratory distress syndrome (ARDS). However, the interaction between Doublecortin-like kinase 1 (DCLK1) and the Hippo signaling pathway in ARDS-associated AECII differentiation remains unclear. Therefore, the objective of this study was to understand the role of the DCLK1/Hippo pathway in mediating AECII differentiation in ARDS. MATERIALS AND METHODS: AECII MLE-12 cells were exposed to 0, 0.1, or 1 μg/mL of lipopolysaccharide (LPS) for 6 and 12 h. In the mouse model, C57BL/6JNarl mice were intratracheally (i.t.) injected with 0 (control) or 5 mg/kg LPS and were euthanized for lung collection on days 3 and 7. RESULTS: We found that LPS induced AECII markers of differentiation by reducing surfactant protein C (SPC) and p53 while increasing T1α (podoplanin) and E-cadherin at 12 h. Concurrently, nuclear YAP dynamic regulation and increased TAZ levels were observed in LPS-exposed AECII within 12 h. Inhibition of YAP consistently decreased cell levels of SPC, claudin 4 (CLDN-4), galectin 3 (LGALS-3), and p53 while increasing transepithelial electrical resistance (TEER) at 6 h. Furthermore, DCLK1 expression was reduced in isolated human AECII of ARDS, consistent with the results in LPS-exposed AECII at 6 h and mouse SPC-positive (SPC+) cells after 3-day LPS exposure. We observed that downregulated DCLK1 increased p-YAP/YAP, while DCLK1 overexpression slightly reduced p-YAP/YAP, indicating an association between DCLK1 and Hippo-YAP pathway. CONCLUSIONS: We conclude that DCLK1-mediated Hippo signaling components of YAP/TAZ regulated markers of AECII-to-AECI differentiation in an LPS-induced ARDS model.
AU  - Chen,X-Y
AU  - Kao,C
AU  - Peng,S-W
AU  - Chang,J-H
AU  - Lee,Y-L
AU  - Laiman,V
AU  - Chung,KF
AU  - Bhavsar,PK
AU  - Heriyanto,DS
AU  - Chuang,K-J
AU  - Chuang,H-C
DO  - 10.1186/s10020-023-00760-0
PY  - 2023///
TI  - Role of DCLK1/Hippo pathway in type II alveolar epithelial cells differentiation in acute respiratory distress syndrome.
T2  - Mol Med
UR  - http://dx.doi.org/10.1186/s10020-023-00760-0
UR  - https://www.ncbi.nlm.nih.gov/pubmed/37996782
VL  - 29
ER  -
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