Wnt5a-mediated autophagy contributes to the epithelial-mesenchymal transition of human bronchial epithelial cells during asthma.
Airway remodeling
Asthma
Autophagy
Calmodulin-dependent kinase II
Epithelial-mesenchymal transition
Wnt5a
Journal
Molecular medicine (Cambridge, Mass.)
ISSN: 1528-3658
Titre abrégé: Mol Med
Pays: England
ID NLM: 9501023
Informations de publication
Date de publication:
19 Jun 2024
19 Jun 2024
Historique:
received:
24
02
2024
accepted:
12
06
2024
medline:
20
6
2024
pubmed:
20
6
2024
entrez:
19
6
2024
Statut:
epublish
Résumé
The epithelial-mesenchymal transition (EMT) of human bronchial epithelial cells (HBECs) is essential for airway remodeling during asthma. Wnt5a has been implicated in various lung diseases, while its role in the EMT of HBECs during asthma is yet to be determined. This study sought to define whether Wnt5a initiated EMT, leading to airway remodeling through the induction of autophagy in HBECs. Microarray analysis was used to investigate the expression change of WNT5A in asthma patients. In parallel, EMT models were induced using 16HBE cells by exposing them to house dust mites (HDM) or interleukin-4 (IL-4), and then the expression of Wnt5a was observed. Using in vitro gain- and loss-of-function approaches via Wnt5a mimic peptide FOXY5 and Wnt5a inhibitor BOX5, the alterations in the expression of the epithelial marker E-cadherin and the mesenchymal marker protein were observed. Mechanistically, the Ca Asthma patients exhibited a significant increase in the gene expression of WNT5A compared to the healthy control. Upon HDM and IL-4 treatments, we observed that Wnt5a gene and protein expression levels were significantly increased in 16HBE cells. Interestingly, Wnt5a mimic peptide FOXY5 significantly inhibited E-cadherin and upregulated α-SMA, Collagen I, and autophagy marker proteins (Beclin1 and LC3-II). Rhodamine-phalloidin staining showed that FOXY5 resulted in a rearrangement of the cytoskeleton and an increase in the quantity of stress fibers in 16HBE cells. Importantly, blocking Wnt5a with BOX5 significantly inhibited autophagy and EMT induced by IL-4 in 16HBE cells. Mechanistically, autophagy inhibitor 3-MA and CaMKII inhibitor KN-93 reduced the EMT of 16HBE cells caused by FOXY5, as well as the increase in stress fibers, cell adhesion, and autophagy. This study illustrates a new link in the Wnt5a-Ca
Sections du résumé
BACKGROUND
BACKGROUND
The epithelial-mesenchymal transition (EMT) of human bronchial epithelial cells (HBECs) is essential for airway remodeling during asthma. Wnt5a has been implicated in various lung diseases, while its role in the EMT of HBECs during asthma is yet to be determined. This study sought to define whether Wnt5a initiated EMT, leading to airway remodeling through the induction of autophagy in HBECs.
METHODS
METHODS
Microarray analysis was used to investigate the expression change of WNT5A in asthma patients. In parallel, EMT models were induced using 16HBE cells by exposing them to house dust mites (HDM) or interleukin-4 (IL-4), and then the expression of Wnt5a was observed. Using in vitro gain- and loss-of-function approaches via Wnt5a mimic peptide FOXY5 and Wnt5a inhibitor BOX5, the alterations in the expression of the epithelial marker E-cadherin and the mesenchymal marker protein were observed. Mechanistically, the Ca
RESULTS
RESULTS
Asthma patients exhibited a significant increase in the gene expression of WNT5A compared to the healthy control. Upon HDM and IL-4 treatments, we observed that Wnt5a gene and protein expression levels were significantly increased in 16HBE cells. Interestingly, Wnt5a mimic peptide FOXY5 significantly inhibited E-cadherin and upregulated α-SMA, Collagen I, and autophagy marker proteins (Beclin1 and LC3-II). Rhodamine-phalloidin staining showed that FOXY5 resulted in a rearrangement of the cytoskeleton and an increase in the quantity of stress fibers in 16HBE cells. Importantly, blocking Wnt5a with BOX5 significantly inhibited autophagy and EMT induced by IL-4 in 16HBE cells. Mechanistically, autophagy inhibitor 3-MA and CaMKII inhibitor KN-93 reduced the EMT of 16HBE cells caused by FOXY5, as well as the increase in stress fibers, cell adhesion, and autophagy.
CONCLUSION
CONCLUSIONS
This study illustrates a new link in the Wnt5a-Ca
Identifiants
pubmed: 38898476
doi: 10.1186/s10020-024-00862-3
pii: 10.1186/s10020-024-00862-3
doi:
Substances chimiques
Wnt-5a Protein
0
WNT5A protein, human
0
Calcium-Calmodulin-Dependent Protein Kinase Type 2
EC 2.7.11.17
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
93Subventions
Organisme : Natural Science Foundation of Hunan Province
ID : 2019JJ40453
Organisme : Health Commission of Hunan Province
ID : 202202014633
Organisme : Health Commission of Hunan Province
ID : D202302019023
Organisme : Health Commission of Hunan Province
ID : B202303028704
Informations de copyright
© 2024. The Author(s).
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