A cGAS-dependent response links DNA damage and senescence in alveolar epithelial cells: a potential drug target in IPF.
A549 Cells
Alveolar Epithelial Cells
/ pathology
Benzofurans
/ pharmacology
Cell Line, Tumor
Cellular Senescence
/ physiology
Cyclin-Dependent Kinase Inhibitor p21
/ genetics
Cytokines
/ biosynthesis
DNA Damage
/ genetics
DNA, Mitochondrial
/ metabolism
Deoxyribonuclease I
/ pharmacology
Epithelial Cell Adhesion Molecule
/ metabolism
Etoposide
/ pharmacology
Humans
Idiopathic Pulmonary Fibrosis
/ pathology
Mitochondria
/ genetics
Nucleotidyltransferases
/ antagonists & inhibitors
RNA Interference
RNA, Small Interfering
/ genetics
Signal Transduction
/ physiology
alveolar epithelium
cGAS
idiopathic pulmonary fibrosis (IPF)
mitochondrial DNA (mtDNA)
senescence
Journal
American journal of physiology. Lung cellular and molecular physiology
ISSN: 1522-1504
Titre abrégé: Am J Physiol Lung Cell Mol Physiol
Pays: United States
ID NLM: 100901229
Informations de publication
Date de publication:
01 11 2021
01 11 2021
Historique:
pubmed:
16
9
2021
medline:
11
11
2021
entrez:
15
9
2021
Statut:
ppublish
Résumé
Alveolar epithelial cell (AEC) senescence is implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Mitochondrial dysfunction including release of mitochondrial DNA (mtDNA) is a feature of senescence, which led us to investigate the role of the DNA-sensing guanine monophosphate-adenine monophosphate (GMP-AMP) synthase (cGAS) in IPF, with a focus on AEC senescence. cGAS expression in fibrotic tissue from lungs of patients with IPF was detected within cells immunoreactive for epithelial cell adhesion molecule (EpCAM) and p21, epithelial and senescence markers, respectively. Submerged primary cultures of AECs isolated from lung tissue of patients with IPF (IPF-AECs,
Identifiants
pubmed: 34524912
doi: 10.1152/ajplung.00574.2020
doi:
Substances chimiques
Benzofurans
0
CDKN1A protein, human
0
Cyclin-Dependent Kinase Inhibitor p21
0
Cytokines
0
DNA, Mitochondrial
0
EPCAM protein, human
0
Epithelial Cell Adhesion Molecule
0
RNA, Small Interfering
0
RU.521
0
Etoposide
6PLQ3CP4P3
Nucleotidyltransferases
EC 2.7.7.-
cGAS protein, human
EC 2.7.7.-
Deoxyribonuclease I
EC 3.1.21.1
Banques de données
figshare
['10.6084/m9.figshare.13262993']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM