Genetic characteristics of the human hepatic stellate cell line LX–2

Weiskirchen, Ralf; Weimer, Jörg; Arnold, Nancy J.; Xu, Liwei; Friedman, SL; Bergmann, Christoph

doi:10.1055/s-0031-1295790

Cited by 2 publications

(2 citation statements)

References 25 publications

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“…The spontaneously immortalized human HSC cell line LX‐2 (provided by Dr. Robert G Bennett, University of Nebraska, with the permission of Dr. Scott Friedman, Icahn School of Medicine at Mount Sinai, New York, NY, USA) (25) was authenticated by American Type Culture Collection (Manassas, VA, USA) using short tandem repeat analysis and matched to the published short tandem repeat loci of LX‐2 (26). Cells were seeded in 6‐well plates in DMEM (Corning, Corning, NY, USA) supplemented with 2% fetal bovine serum (Atlanta Biologicals, Flowery Branch, GA, USA).…”

Section: Methodsmentioning

confidence: 99%

Therapeutic effects of a small molecule agonist of the relaxin receptor ML290 in liver fibrosis

Kaftanovskaya

Soula

et al. 2019

The FASEB Journal

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Fibrosis is an underlying cause of cirrhosis and hepatic failure resulting in end stage liver disease with limited pharmacological options. The beneficial effects of relaxin peptide treatment were demonstrated in clinically relevant animal models of liver fibrosis. However, the use of relaxin is problematic because of a short half‐life. The aim of this study was to test the therapeutic effects of recently identified small molecule agonists of the human relaxin receptor, relaxin family peptide receptor 1 (RXFP1). The lead compound of this series, ML290, was selected based on its effects on the expression of fibrosis‐related genes in primary human stellate cells. RNA sequencing analysis of TGF‐β1–activated LX‐2 cells showed that ML290 treatment primarily affected extracellular matrix remodeling and cytokine signaling, with expression profiles indicating an antifibrotic effect of ML290. ML290 treatment in human liver organoids with LPS‐induced fibrotic phenotype resulted in a significant reduction of type I collagen. The pharmacokinetics of ML290 in mice demonstrated its high stability in vivo, as evidenced by the sustained concentrations of compound in the liver. In mice expressing human RXFP1 gene treated with carbon tetrachloride, ML290 significantly reduced collagen content, α‐smooth muscle actin expression, and cell proliferation around portal ducts. In conclusion, ML290 demonstrated antifibrotic effects in liver fibrosis.—Kaftanovskaya, E. M., Ng, H. H., Soula, M., Rivas, B., Myhr, C., Ho, B. A., Cervantes, B. A., Shupe, T. D., Devarasetty, M., Hu, X., Xu, X., Patnaik, S., Wilson, K. J., Barnaeva, E., Ferrer, M., Southall, N. T., Marugan, J. J., Bishop, C. E., Agoulnik, I. U., Agoulnik, A. I. Therapeutic effects of a small molecule agonist of the relaxin receptor ML290 in liver fibrosis. FASEB J. 33, 12435–12446 (2019). http://www.fasebj.org

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Section: Methodsmentioning

confidence: 99%

Therapeutic effects of a small molecule agonist of the relaxin receptor ML290 in liver fibrosis

Kaftanovskaya

Soula

et al. 2019

The FASEB Journal

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show abstract

“…The authors further found that the transient overexpression of SHP or the incubation with AICAR or metformin diminished the HCV‐associated activation of NF‐κB as well as the production of TGF‐β and connective tissue growth factor (CTGF/CCN2), again demonstrating the antifibrotic potential of SHP. Moreover, the overexpression of SHP and activation of AMPK ameliorated HSC invasion in a co‐culture system with the genetically well‐characterized immortalized human hepatic stellate cell line LX‐2 .…”

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confidence: 99%