Tag Archives: hepatic stellate cells

YAP/TAZ Suppress Drug Penetration into Hepatocellular Carcinoma via Stromal Activation

Multi-cellular hepatocellular carcinoma (HCC) organoid models were established which contained various types of stromal cells, such as hepatic stellate cells, fibroblasts, and endothelial cells together with HCC cells.
[Hepatology]
Cho, K., Ro, S. W., Lee, H. W., Moon, H., Han, S., Kim, H. R., Ahn, S. H., Park, J. Y., & Kim, D. Y. (n.d.). YAP/TAZ suppress drug penetration into hepatocellular carcinoma via stromal activation. Hepatology, n/a(n/a). https://doi.org/10.1002/hep.32000 Cite
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Liver Regeneration and Inflammation: From Fundamental Science to Clinical Applications

The authors describe the mechanisms of tissue repair following damage, highlighting the close relationship between inflammation and liver regeneration, and discuss how recent findings can help design novel therapeutic approaches.
[Nature Reviews Molecular Cell Biology]
Campana, L., Esser, H., Huch, M., & Forbes, S. (2021). Liver regeneration and inflammation: from fundamental science to clinical applications. Nature Reviews Molecular Cell Biology, 1–17. https://doi.org/10.1038/s41580-021-00373-7 Cite
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Hepatic Stellate Cells Suppress NK Cell-Sustained Breast Cancer Dormancy

The proteomics studies on liver co-cultures implicated the activated hepatic stellate cells-secreted chemokine CXCL12 in the induction of NK cell quiescence through its cognate receptor CXCR4.
[Nature]
Correia, A. L., Guimaraes, J. C., Auf der Maur, P., De Silva, D., Trefny, M. P., Okamoto, R., Bruno, S., Schmidt, A., Mertz, K., Volkmann, K., Terracciano, L., Zippelius, A., Vetter, M., Kurzeder, C., Weber, W. P., & Bentires-Alj, M. (2021). Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy. Nature, 1–6. https://doi.org/10.1038/s41586-021-03614-z Cite
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Identification of Hepatic Fibrosis Inhibitors through Morphometry Analysis of a Hepatic Multicellular Spheroids Model

Scientists established liver fibrosis models using multicellular tumor spheroids (MCTSs) composed of hepatocellular carcinoma (HCC) and stromal cells such as fibroblasts (WI38), hepatic stellate cells (LX2), and endothelial cells (HUVEC) seeded at constant ratios.
[Scientific Reports]
Song, Y., Kim, S., Heo, J., Shum, D., Lee, S.-Y., Lee, M., Kim, A.-R., & Seo, H. R. (2021). Identification of hepatic fibrosis inhibitors through morphometry analysis of a hepatic multicellular spheroids model. Scientific Reports, 11(1), 10931. https://doi.org/10.1038/s41598-021-90263-x Cite
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Human Placental Mesenchymal Stem Cells Ameliorate Liver Fibrosis in Mice by Upregulation of Caveolin1 in Hepatic Stellate Cells

The authors established mouse models of CCl4-injured liver fibrosis (LF) and administered hPMSCs at different stages of LF once a week for two weeks. The therapeutic effect of hPMSCs on LF was investigated, according to histopathological and blood biochemical analyses.
[Stem Cell Research & Therapy]
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Inhibiting xCT/SLC7A11 Induces Ferroptosis of Myofibroblastic Hepatic Stellate Cells but Exacerbates Chronic Liver Injury

Investigators evaluated the hypothesis that myofibroblastic (activated) hepatic stellate cells and liver fibrosis could be safely reduced by inhibiting the cysteine/glutamate antiporter xCT.
[Liver International]
Du, K., Oh, S. H., Dutta, R. K., Sun, T., Yang, W.-H., Chi, J.-T. A., & Diehl, A. M. (n.d.). Inhibiting xCT/SLC7A11 induces ferroptosis of myofibroblastic hepatic stellate cells but exacerbates chronic liver injury. Liver International, n/a(n/a). https://doi.org/https://doi.org/10.1111/liv.14945 Cite
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Fas/FasL Mediates NF-κBp65/PUMA-Modulated Hepatocytes Apoptosis via Autophagy to Drive Liver Fibrosis

Researchers investigated the Fas/FasL signaling and hepatocytes apoptosis in liver samples from both human sections and mouse models.
[Cell Death & Disease]
Tan, S., Liu, X., Chen, L., Wu, X., Tao, L., Pan, X., Tan, S., Liu, H., Jiang, J., & Wu, B. (2021). Fas/FasL mediates NF-κBp65/PUMA-modulated hepatocytes apoptosis via autophagy to drive liver fibrosis. Cell Death & Disease, 12(5), 1–18. https://doi.org/10.1038/s41419-021-03749-x Cite
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Mechanisms and Disease Consequences of Nonalcoholic Fatty Liver Disease

Investigators provide an in-depth discussion of the underlying pathogenetic mechanisms that lead to progressive liver injury, including the metabolic origins of Nonalcoholic fatty liver disease (NAFLD), the effect of NAFLD on hepatic glucose and lipid metabolism, bile acid toxicity, macrophage dysfunction, and hepatic stellate cell activation, and consider the role of genetic, epigenetic, and environmental factors that promote fibrosis progression and risk of hepatocellular carcinoma in nonalcoholic steatohepatitis.
[Cell]
Loomba, R., Friedman, S. L., & Shulman, G. I. (2021). Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell, 184(10), 2537–2564. https://doi.org/10.1016/j.cell.2021.04.015 Cite
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Activation of Transmembrane Receptor Tyrosine Kinase DDR1-STAT3 Cascade by Extracellular Matrix Remodeling Promotes Liver Metastatic Colonization in Uveal Melanoma

The authors postulated the hypothesis that DDR1 and its ligand might ignite the interaction between uveal melanoma (UM) cells and their surrounding niche of liver thereby conferring strengthened survival, proliferation, stemness and eventually promoting metastatic colonization in liver.
[Signal Transduction and Targeted Therapy]
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Glucocorticoid-Induced Leucine Zipper Regulates Liver Fibrosis by Suppressing CCL2-Mediated Leukocyte Recruitment

Investigators found that glucocorticoid-induced leucine zipper deficiency in mice was associated with elevated CCL2 production and pro-inflammatory leukocyte infiltration at the early liver fibrosis (LF) stage, resulting in enhanced LF development.
[Cell Death & Disease]
Flamini, S., Sergeev, P., Viana de Barros, Z., Mello, T., Biagioli, M., Paglialunga, M., Fiorucci, C., Prikazchikova, T., Pagano, S., Gagliardi, A., Riccardi, C., Zatsepin, T., Migliorati, G., Bereshchenko, O., & Bruscoli, S. (2021). Glucocorticoid-induced leucine zipper regulates liver fibrosis by suppressing CCL2-mediated leukocyte recruitment. Cell Death & Disease, 12(5), 1–13. https://doi.org/10.1038/s41419-021-03704-w Cite
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SAA1/TLR2 Axis Directs Chemotactic Migration of Hepatic Stellate Cells Responding to Injury

Scientists demonstrated that serum amyloid A1 (SAA1) acts as a chemokine recruiting HSCs towards injury loci signaling via TLR2, a finding proven by gene manipulation studies in cell and mice models.
[iScience]
Getachew, A., Abbas, N., You, K., Yang, Z., Hussain, M., Huang, X., Cheng, Z., Tan, S., Tao, J., Yu, X., Chen, Y., Yang, F., Pan, T., Xu, Y., Xu, G., Zhuang, Y., Wu, F., & Li, Y. (2021). SAA1/TLR2 axis directs chemotactic migration of hepatic stellate cells responding to injury. IScience, 0(0). https://doi.org/10.1016/j.isci.2021.102483 Cite
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