SIRT1 Deficiency, Specifically in Fibroblasts, Decreases Apoptosis Resistance and Is Associated with Resolution of Lung-Fibrosis.
Acetylation
/ drug effects
Animals
Bleomycin
/ adverse effects
CASP8 and FADD-Like Apoptosis Regulating Protein
/ antagonists & inhibitors
Cell Line
Cell Survival
/ drug effects
Disease Models, Animal
Down-Regulation
Fibroblasts
/ cytology
Gene Knockout Techniques
Humans
Ku Autoantigen
/ metabolism
Lung
/ cytology
Male
Mice
MicroRNAs
/ genetics
Organ Specificity
Pulmonary Fibrosis
/ chemically induced
RNA, Small Interfering
/ pharmacology
Sirtuin 1
/ metabolism
FLIP
IPF-resolution
Ku70
SIRT1
cell-death
myofibroblasts
Journal
Biomolecules
ISSN: 2218-273X
Titre abrégé: Biomolecules
Pays: Switzerland
ID NLM: 101596414
Informations de publication
Date de publication:
02 07 2020
02 07 2020
Historique:
received:
07
05
2020
revised:
16
06
2020
accepted:
29
06
2020
entrez:
8
7
2020
pubmed:
8
7
2020
medline:
20
4
2021
Statut:
epublish
Résumé
In contrast to normal regenerating tissue, resistance to Fas- and FasL-positive T cell-induced apoptosis were detected in myofibroblasts from fibrotic-lungs of humans and mice following bleomycin (BLM) exposure. In this study we show, decreased FLIP expression in lung-tissues with resolution of BLM-induced fibrosis and in isolated-lung fibroblasts, with decreased resistance to apoptosis. Using a FLIP-expression vector or a shFLIP-RNA, we further confirmed the critical need for FLIP to regain/lose susceptibility of fibrotic-lung myofibroblast to Fas-induced apoptosis. Our study further show that FLIP is regulated by SIRT1 (Sirtuin 1) deacetylase. Chimeric mice, with SIRT1-deficiency in deacetylase domain (
Identifiants
pubmed: 32630813
pii: biom10070996
doi: 10.3390/biom10070996
pmc: PMC7407379
pii:
doi:
Substances chimiques
CASP8 and FADD-Like Apoptosis Regulating Protein
0
CFLAR protein, human
0
MIRN34 microRNA, human
0
MicroRNAs
0
RNA, Small Interfering
0
Bleomycin
11056-06-7
SIRT1 protein, human
EC 3.5.1.-
Sirtuin 1
EC 3.5.1.-
Xrcc6 protein, human
EC 3.6.4.12
Ku Autoantigen
EC 4.2.99.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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