Nanchangmycin regulates FYN, PTK2, and MAPK1/3 to control the fibrotic activity of human hepatic stellate cells.
FYN
cell biology
collagen
compound screening
hepatic stellate cells
human
liver fibrosis
nanchangmycin
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
26 05 2022
26 05 2022
Historique:
received:
07
10
2021
accepted:
06
05
2022
entrez:
26
5
2022
pubmed:
27
5
2022
medline:
31
5
2022
Statut:
epublish
Résumé
Chronic liver injury causes fibrosis, characterized by the formation of scar tissue resulting from excessive accumulation of extracellular matrix (ECM) proteins. Hepatic stellate cell (HSC) myofibroblasts are the primary cell type responsible for liver fibrosis, yet there are currently no therapies directed at inhibiting the activity of HSC myofibroblasts. To search for potential anti-fibrotic compounds, we performed a high-throughput compound screen in primary human HSC myofibroblasts and identified 19 small molecules that induce HSC inactivation, including the polyether ionophore nanchangmycin (NCMC). NCMC induces lipid re-accumulation while reducing collagen expression, deposition of collagen in the extracellular matrix, cell proliferation, and migration. We find that NCMC increases cytosolic Ca
Identifiants
pubmed: 35617485
doi: 10.7554/eLife.74513
pii: 74513
pmc: PMC9135407
doi:
pii:
Substances chimiques
Ethers
0
Extracellular Matrix Proteins
0
Spiro Compounds
0
nanchangmycin
0
Collagen
9007-34-5
Focal Adhesion Kinase 1
EC 2.7.10.2
PTK2 protein, human
EC 2.7.10.2
MAPK1 protein, human
EC 2.7.11.24
Mitogen-Activated Protein Kinase 1
EC 2.7.11.24
Banques de données
GEO
['GSE78853']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK043351
Pays : United States
Informations de copyright
© 2022, Li et al.
Déclaration de conflit d'intérêts
WL, JC, CS, RS, LP, RR, SM, JP, RK, DW, SH No competing interests declared, MB MB is an employee of Boehringer Ingelheim, AS AS is an employee of Boehringer Ingelheim, JD JFD is an employee of Boehringer Ingelheim, JR JFR is an employee of Boehringer Ingelheim, AM ACM receives funding from Bristol-Myers Squibb and GlaxoSmithKline for unrelated projects and is a consultant for Circ Bio and Third Rock Ventures
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