Kasugamycin Is a Novel Chitinase 1 Inhibitor with Strong Antifibrotic Effects on Pulmonary Fibrosis.
TGF-β
TGFBRAP1
chitinase 1
kasugamycin
pulmonary fibrosis
Journal
American journal of respiratory cell and molecular biology
ISSN: 1535-4989
Titre abrégé: Am J Respir Cell Mol Biol
Pays: United States
ID NLM: 8917225
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
pubmed:
10
6
2022
medline:
9
9
2022
entrez:
9
6
2022
Statut:
ppublish
Résumé
Pulmonary fibrosis is a devastating lung disease with few therapeutic options. CHIT1 (chitinase 1), an 18 glycosyl hydrolase family member, contributes to the pathogenesis of pulmonary fibrosis through the regulation of TGF-β (transforming growth factor-β) signaling and effector function. Therefore, CHIT1 is a potential therapeutic target for pulmonary fibrosis. This study aimed to identify and characterize a druggable CHIT1 inhibitor with strong antifibrotic activity and minimal toxicity for therapeutic application to pulmonary fibrosis. Extensive screening of small molecule libraries identified the aminoglycoside antibiotic kasugamycin (KSM) as a potent CHIT1 inhibitor. Elevated concentrations of CHIT1 were detected in the lungs of patients with pulmonary fibrosis. In
Identifiants
pubmed: 35679109
doi: 10.1165/rcmb.2021-0156OC
pmc: PMC9447144
doi:
Substances chimiques
Aminoglycosides
0
Antifibrotic Agents
0
Transforming Growth Factor beta
0
Bleomycin
11056-06-7
Chitinases
EC 3.2.1.14
kasugamycin
O957UYB9DY
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
309-319Subventions
Organisme : NHLBI NIH HHS
ID : P01 HL114501
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL115813
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL155558
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Références
Antimicrob Agents Chemother (Bethesda). 1965;5:753-7
pubmed: 5883494
Chem Biol. 2005 Sep;12(9):973-80
pubmed: 16183021
J Urol. 1967 May;97(5):917-25
pubmed: 4961002
Hinyokika Kiyo. 1968 Jan;14(1):50-6
pubmed: 4971183
Genetics. 2007 Oct;177(2):959-70
pubmed: 17720922
Pharmacoeconomics. 2017 Apr;35(4):479-491
pubmed: 28039616
N Engl J Med. 2019 Jun 27;380(26):2518-2528
pubmed: 31112379
J Exp Med. 2004 Aug 2;200(3):377-89
pubmed: 15289506
Eur Respir J. 2004 Jul;24(1):57-65
pubmed: 15293605
Curr Pathobiol Rep. 2017 Jun;5(2):101-110
pubmed: 29082111
Nat Prod Rep. 2007 Apr;24(2):358-92
pubmed: 17390001
Life Sci Alliance. 2019 May 13;2(3):
pubmed: 31085559
J Immunol. 2012 Sep 1;189(5):2635-44
pubmed: 22826322
Am J Respir Cell Mol Biol. 1996 Feb;14(2):131-8
pubmed: 8630262
BMC Evol Biol. 2007 Jun 26;7:96
pubmed: 17594485
Chest. 2002 Dec;122(6 Suppl):289S-293S
pubmed: 12475802
J Biol Chem. 2001 Jun 1;276(22):19495-502
pubmed: 11278302
Appl Microbiol. 1967 Jul;15(4):750-3
pubmed: 6049299
Am J Respir Crit Care Med. 2011 Feb 15;183(4):431-40
pubmed: 20935110
Front Pharmacol. 2014 Jan 23;5:2
pubmed: 24478703
Front Physiol. 2017 Mar 15;8:159
pubmed: 28360865
J Antibiot (Tokyo). 1965 Mar;18:104-6
pubmed: 14326081
Thorax. 2001 Dec;56(12):907-15
pubmed: 11713352
JCI Insight. 2018 Sep 20;3(18):
pubmed: 30232270
Sci Rep. 2017 Jun 5;7(1):2768
pubmed: 28584264
Annu Rev Physiol. 2011;73:479-501
pubmed: 21054166
J Clin Invest. 1994 Mar;93(3):1288-92
pubmed: 8132768
Eur J Pharmacol. 2008 Aug 20;590(1-3):400-8
pubmed: 18598692
Am J Physiol Lung Cell Mol Physiol. 2003 Sep;285(3):L527-39
pubmed: 12598227
Ther Adv Chronic Dis. 2019 Jul 18;10:2040622319862697
pubmed: 31367296
Chest. 2000 Sep;118(3):788-94
pubmed: 10988204
J Antibiot B. 1967 Jun;20(3):175-8
pubmed: 4965580
Ther Clin Risk Manag. 2016 Apr 08;12:563-74
pubmed: 27114711
J Antibiot (Tokyo). 1965 Mar;18:107-10
pubmed: 14326082
Elife. 2018 Aug 28;7:
pubmed: 30152756
Ann Intern Med. 2001 Jan 16;134(2):136-51
pubmed: 11177318