DMBT1 is upregulated in lung epithelial cells after hypoxia and changes surfactant ultrastructure.
Biological Products
/ administration & dosage
Calcium-Binding Proteins
/ genetics
Cell Line
DNA-Binding Proteins
/ genetics
Epithelial Cells
/ metabolism
Humans
Hypoxia
/ genetics
Infant, Newborn
Lung
/ cytology
Phospholipids
/ administration & dosage
Pulmonary Surfactants
/ administration & dosage
Respiratory Distress Syndrome, Newborn
/ genetics
Tumor Suppressor Proteins
/ genetics
Up-Regulation
DMBT1
hypoxia
lung epithelial cells
surfactant
Journal
Pediatric pulmonology
ISSN: 1099-0496
Titre abrégé: Pediatr Pulmonol
Pays: United States
ID NLM: 8510590
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
18
05
2020
accepted:
05
08
2020
pubmed:
10
8
2020
medline:
25
2
2021
entrez:
10
8
2020
Statut:
ppublish
Résumé
Hypoxia and asphyxia are known to induce surfactant inactivation in newborns. Deleted in Malignant Brain Tumors 1 (DMBT1) is an innate immunity protein with functions in epithelial differentiation and angiogenesis. It was detected in hyaline membranes of infants with respiratory distress syndrome. Human recombinant DMBT1 is able to increase the surface tension of exogenous surfactant preparations in a dose-dependent manner. Immunohistochemistry was performed on lung sections of infants who died due to pre-, peri- or postnatal hypoxia. The lung epithelial cell line A549 was stably transfected with a DMBT1 (DMBT1+ cells) expression plasmid or with an empty plasmid (DMBT1- cells). The cells were cultured in normoxic or hypoxic conditions, and then DMBT1 as well as HIF-1α RNA expression were analyzed by using real-time-polymerase chain reaction. Human recombinant DMBT1 was added to the modified porcine natural surfactant Curosurf to examine the effect of DMBT1 on surfactant ultrastructure with electron microscopy. DMBT1 expression was upregulated in human lung tissue after fetal/peri-/postnatal hypoxia. In addition, in vitro experiments showed increased DMBT1 RNA expression in A549 cells after hypoxia. HIF-1α was upregulated in both DMBT1+ and DMBT1- cells in response to hypoxia. The addition of human recombinant DMBT1 to Curosurf caused an impaired surfactant ultrastructure. DMBT1 is upregulated in response to hypoxia and there seems to be a link between hypoxia and surfactant inactivation.
Sections du résumé
BACKGROUND
Hypoxia and asphyxia are known to induce surfactant inactivation in newborns. Deleted in Malignant Brain Tumors 1 (DMBT1) is an innate immunity protein with functions in epithelial differentiation and angiogenesis. It was detected in hyaline membranes of infants with respiratory distress syndrome. Human recombinant DMBT1 is able to increase the surface tension of exogenous surfactant preparations in a dose-dependent manner.
METHODS
Immunohistochemistry was performed on lung sections of infants who died due to pre-, peri- or postnatal hypoxia. The lung epithelial cell line A549 was stably transfected with a DMBT1 (DMBT1+ cells) expression plasmid or with an empty plasmid (DMBT1- cells). The cells were cultured in normoxic or hypoxic conditions, and then DMBT1 as well as HIF-1α RNA expression were analyzed by using real-time-polymerase chain reaction. Human recombinant DMBT1 was added to the modified porcine natural surfactant Curosurf to examine the effect of DMBT1 on surfactant ultrastructure with electron microscopy.
RESULTS
DMBT1 expression was upregulated in human lung tissue after fetal/peri-/postnatal hypoxia. In addition, in vitro experiments showed increased DMBT1 RNA expression in A549 cells after hypoxia. HIF-1α was upregulated in both DMBT1+ and DMBT1- cells in response to hypoxia. The addition of human recombinant DMBT1 to Curosurf caused an impaired surfactant ultrastructure.
CONCLUSIONS
DMBT1 is upregulated in response to hypoxia and there seems to be a link between hypoxia and surfactant inactivation.
Substances chimiques
Biological Products
0
Calcium-Binding Proteins
0
DMBT1 protein, human
0
DNA-Binding Proteins
0
Phospholipids
0
Pulmonary Surfactants
0
Tumor Suppressor Proteins
0
poractant alfa
KE3U2023NP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2964-2969Informations de copyright
© 2020 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.
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