The Sphingosine Kinase 1 Inhibitor, PF543, Mitigates Pulmonary Fibrosis by Reducing Lung Epithelial Cell mtDNA Damage and Recruitment of Fibrogenic Monocytes.
Adaptor Proteins, Signal Transducing
/ antagonists & inhibitors
Alveolar Epithelial Cells
/ drug effects
Animals
Asbestos
/ toxicity
Bleomycin
/ pharmacology
DNA Damage
/ drug effects
DNA, Mitochondrial
/ drug effects
Humans
Idiopathic Pulmonary Fibrosis
/ drug therapy
Lung
/ drug effects
Methanol
/ analogs & derivatives
Mice
Mitochondria
/ drug effects
Monocytes
/ drug effects
Pulmonary Fibrosis
/ chemically induced
Pyrrolidines
/ pharmacology
Signal Transduction
/ drug effects
Sulfones
SPHK1
alveolar epithelial cell
monocytes
mtDNA damage
oxidative stress
pulmonary fibrosis
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
05 Aug 2020
05 Aug 2020
Historique:
received:
15
07
2020
revised:
31
07
2020
accepted:
02
08
2020
entrez:
9
8
2020
pubmed:
9
8
2020
medline:
18
2
2021
Statut:
epublish
Résumé
Idiopathic pulmonary fibrosis (IPF) is a chronic disease for which novel approaches are urgently required. We reported increased sphingosine kinase 1 (SPHK1) in IPF lungs and that SPHK1 inhibition using genetic and pharmacologic approaches reduces murine bleomycin-induced pulmonary fibrosis. We determined whether PF543, a specific SPHK1 inhibitor post bleomycin or asbestos challenge mitigates lung fibrosis by reducing mitochondrial (mt) DNA damage and pro-fibrotic monocyte recruitment-both are implicated in the pathobiology of pulmonary fibrosis. Bleomycin (1.5 U/kg), crocidolite asbestos (100 µg/50 µL) or controls was intratracheally instilled in Wild-Type (
Identifiants
pubmed: 32764262
pii: ijms21165595
doi: 10.3390/ijms21165595
pmc: PMC7460639
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
DNA, Mitochondrial
0
PF-543
0
Pyrrolidines
0
SPHKAP protein, human
0
Sulfones
0
Bleomycin
11056-06-7
Asbestos
1332-21-4
Methanol
Y4S76JWI15
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : CSRD VA
ID : I01 CX001777
Pays : United States
Organisme : United States Veterans Administration
ID : 2IO1BX000786-05A2
Organisme : National Institutes of Health/ HLBI (Project 3)
ID : HL 126609
Organisme : NIA NIH HHS
ID : P01 AG049665
Pays : United States
Organisme : National Institute of Health
ID : 5R21AG060211-02
Organisme : NCI NIH HHS
ID : P30-CA060553
Pays : United States
Organisme : National Institutes of Health/HLBI (Project 4)
ID : P01 Hl 060678
Organisme : NIH HHS
ID : RO1 HL127342
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL134800
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL060678
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG060211
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL126609
Pays : United States
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