Alteration in branching morphogenesis via YAP/TAZ in fibroblasts of fetal lungs in an LPS-induced inflammation model.
Female
Humans
Infant, Newborn
Cell Cycle Proteins
/ metabolism
Chorioamnionitis
Fibroblasts
/ metabolism
Inflammation
/ metabolism
Interleukin-6
/ metabolism
Interleukin-8
/ metabolism
Lipopolysaccharides
Lung
/ metabolism
Morphogenesis
Premature Birth
/ metabolism
RNA
/ metabolism
Sirtuin 1
/ metabolism
Trans-Activators
/ genetics
Pregnancy
Fibroblast
Hippo signaling pathway
Inflammation
Morphogenesis
Pseudoglandular stage
Journal
Molecular medicine (Cambridge, Mass.)
ISSN: 1528-3658
Titre abrégé: Mol Med
Pays: England
ID NLM: 9501023
Informations de publication
Date de publication:
30 01 2023
30 01 2023
Historique:
received:
02
08
2022
accepted:
23
01
2023
entrez:
30
1
2023
pubmed:
31
1
2023
medline:
2
2
2023
Statut:
epublish
Résumé
Chorioamnionitis is a common cause of preterm birth and leads to serious complications in newborns. The objective of this study was to investigate the role of the Hippo signaling pathway in lung branching morphogenesis under a lipopolysaccharide (LPS)-induced inflammation model. IMR-90 cells and ex vivo fetal lungs were treated with 0, 10, 30, or 50 μg/ml LPS for 24 and 72 h. Supernatant levels of lactate dehydrogenase (LDH), interleukin (IL)-6, IL-8, Chemokine (C-X-C motif) ligand 1(CXCL1), branching and the surface area ratio, Yes-associated protein (YAP), transcription coactivator with PDZ-binding motif (TAZ), fibroblast growth factor 10 (FGF10), fibroblast growth factor receptor II (FGFR2), SRY-box transcription factor 2 (SOX2), SOX9, and sirtuin 1 (SIRT1) levels were examined. Differentially expressed genes in fetal lungs after LPS treatment were identified by RNA-sequencing. LPS at 50 μg/ml increased IL-6 and IL-8 in IMR-90 cells and increased IL-6, CXCL1 and LDH in fetal lungs. The branching ratio significantly increased by LPS at 30 μg/ml compared to the control but the increased level had decreased by 50 μg/ml LPS exposure. Exposure to 50 μg/ml LPS increased phosphorylated (p)-YAP, p-YAP/YAP, and p-TAZ/TAZ in IMR-90 cells, whereas 50 μg/ml LPS decreased FGF10 and SOX2. Consistently, p-YAP/YAP and p-TAZ/TAZ were increased in fibronectin This study showed that regulation of the Hippo pathway in fibroblasts of fetal lungs was involved in branching morphogenesis under an inflammatory disease such as chorioamnionitis.
Sections du résumé
BACKGROUND
Chorioamnionitis is a common cause of preterm birth and leads to serious complications in newborns. The objective of this study was to investigate the role of the Hippo signaling pathway in lung branching morphogenesis under a lipopolysaccharide (LPS)-induced inflammation model.
MATERIALS AND METHODS
IMR-90 cells and ex vivo fetal lungs were treated with 0, 10, 30, or 50 μg/ml LPS for 24 and 72 h. Supernatant levels of lactate dehydrogenase (LDH), interleukin (IL)-6, IL-8, Chemokine (C-X-C motif) ligand 1(CXCL1), branching and the surface area ratio, Yes-associated protein (YAP), transcription coactivator with PDZ-binding motif (TAZ), fibroblast growth factor 10 (FGF10), fibroblast growth factor receptor II (FGFR2), SRY-box transcription factor 2 (SOX2), SOX9, and sirtuin 1 (SIRT1) levels were examined. Differentially expressed genes in fetal lungs after LPS treatment were identified by RNA-sequencing.
RESULTS
LPS at 50 μg/ml increased IL-6 and IL-8 in IMR-90 cells and increased IL-6, CXCL1 and LDH in fetal lungs. The branching ratio significantly increased by LPS at 30 μg/ml compared to the control but the increased level had decreased by 50 μg/ml LPS exposure. Exposure to 50 μg/ml LPS increased phosphorylated (p)-YAP, p-YAP/YAP, and p-TAZ/TAZ in IMR-90 cells, whereas 50 μg/ml LPS decreased FGF10 and SOX2. Consistently, p-YAP/YAP and p-TAZ/TAZ were increased in fibronectin
CONCLUSIONS
This study showed that regulation of the Hippo pathway in fibroblasts of fetal lungs was involved in branching morphogenesis under an inflammatory disease such as chorioamnionitis.
Identifiants
pubmed: 36717779
doi: 10.1186/s10020-023-00613-w
pii: 10.1186/s10020-023-00613-w
pmc: PMC9887856
doi:
Substances chimiques
Cell Cycle Proteins
0
Interleukin-6
0
Interleukin-8
0
Lipopolysaccharides
0
RNA
63231-63-0
Sirtuin 1
EC 3.5.1.-
Trans-Activators
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
16Informations de copyright
© 2023. The Author(s).
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