@article {10.7554/eLife.74513,
	title = {Nanchangmycin regulates FYN, PTK2, and MAPK1/3 to control the fibrotic activity of human hepatic stellate cells},
	journal = {eLife},
	volume = {11},
	year = {2022},
	month = {may},
	pages = {e74513},
	publisher = {eLife Sciences Publications, Ltd},
	abstract = {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\textsuperscript2+ and reduces the phosphorylated protein levels of FYN, PTK2 (FAK), MAPK1/3 (ERK2/1), HSPB1 (HSP27), and STAT5B. Further, depletion of each of these kinases suppress \textitCOL1A1 expression. These studies reveal a signaling network triggered by NCMC to inactivate HSC myofibroblasts and reduce expression of proteins that compose the fibrotic scar. Identification of the antifibrotic effects of NCMC and the elucidation of pathways by which NCMC inhibits fibrosis provide new tools and therapeutic targets that could potentially be utilized to combat the development and progression of liver fibrosis.},
	keywords = {Collagen, compound screening, FYN, Hepatic Stellate Cells, liver fibrosis, nanchangmycin},
	issn = {2050-084X},
	doi = {10.7554/eLife.74513},
	url = {https://doi.org/10.7554/eLife.74513},
	author = {Li, Wenyang and Chen, Jennifer Y and Sun, Cheng and Sparks, Robert P and Pantano, Lorena and Rahman, Raza-Ur and Moran, Sean P and Pondick, Joshua V and Rory Kirchner and Wrobel, David and Bieler, Michael and Sauer, Achim and Ho Sui, Shannan J and Doerner, Julia F and Rippmann, J{\"o}rg F and Mullen, Alan C},
	editor = {Quinn, Matthew A and Cooper, Jonathan A and Sancho-Bru, Pau}
}
