Proline-Rich Tyrosine Kinase 2 Mediates Transforming Growth Factor-Beta-Induced Hepatic Stellate Cell Activation and Liver Fibrosis

The impact of ECM on TGF-β-mediated fibrogenic signaling pathway in hepatic stellate cells (HSCs) has remained obscure. Investigators studied the role of non-receptor tyrosine kinase focal adhesion kinase family members in TGF-β-signaling in HSCs.
[Scientific Reports]
Kim, J., Kang, W., Kang, S. H., Park, S. H., Kim, J. Y., Yang, S., Ha, S. Y., & Paik, Y.-H. (2020). Proline-rich tyrosine kinase 2 mediates transforming growth factor-beta-induced hepatic stellate cell activation and liver fibrosis. Scientific Reports, 10(1), 21018. https://doi.org/10.1038/s41598-020-78056-0 Cite
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The Power of Plasticity- Metabolic Regulation of Hepatic Stellate Cells

To support their functions in health and disease, hepatic stellate cells (HSCs) engage pathways regulating carbohydrate, mitochondrial, lipid, and retinoid homeostasis. In chronic liver injury, HSCs drive hepatic fibrosis and are implicated in inflammation and cancer.
[Cell Metabolism]
Trivedi, P., Wang, S., & Friedman, S. L. (2020). The Power of Plasticity—Metabolic Regulation of Hepatic Stellate Cells. Cell Metabolism. https://doi.org/10.1016/j.cmet.2020.10.026 Cite
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Manipulating the Tumor Microenvironment in Tumor Organoids Induces Phenotypic Changes and Chemoresistance

Investigators used a tumor organoid model, consisting of hepatic stellate cells embedded in Collagen-1 (Col1) and colorectal cancer cell (HCT-116) spheroids, to determine the relationship between the ECM architecture, cancer cell malignancy, and chemoresistance.
[iScience]
Dominijanni, A., Devarasetty, M., & Soker, S. (2020). Manipulating the Tumor Microenvironment in Tumor Organoids Induces Phenotypic Changes and Chemoresistance. IScience, 0(0). https://doi.org/10.1016/j.isci.2020.101851 Cite
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Organoids and Spheroids As Novel Models for Studying Cholestatic Liver Injury and Cholangiocarcinoma

The authors summarize current methodologies for organoid/spheroid formation and a potential for 3D hepatic cell cultures as novel in vitro models of cholangiopathies.
[Hepatology]
Organoids and spheroids as novel models for studying cholestatic liver injury and cholangiocarcinoma - Sato - - Hepatology - Wiley Online Library. (n.d.). Retrieved November 24, 2020, from https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.31653 Cite
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Regulation of Peroxisome Proliferator-Activated Receptor-Gamma Activity Affects the Hepatic Stellate Cell Activation and the Progression of NASH via TGF-β1/Smad Signaling Pathway

PAR-γ agonist was found to inhibit primary HSCs and NIH/3T3 fibroblast activation and reverted their phenotypical morphology induced by TGF-β1 in vitro. In addition to this, PPAR-γ agonist decreased expression of TGF-β1 and phosphorylation of Smad2/3 while increased expression of Smad7.
[Journal of Physiology and Biochemistry]
Ni, X.-X., Li, X.-Y., Wang, Q., & Hua, J. (2020). Regulation of peroxisome proliferator-activated receptor-gamma activity affects the hepatic stellate cell activation and the progression of NASH via TGF-β1/Smad signaling pathway. Journal of Physiology and Biochemistry. https://doi.org/10.1007/s13105-020-00777-7 Cite
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AdipoR1/AdipoR2 Dual Agonist Recovers Nonalcoholic Steatohepatitis and Related Fibrosis via Endoplasmic Reticulum-Mitochondria Axis

Investigators synthesized and reported an adiponectin-based agonist JT003, which potently improved insulin resistance in high fat diet induced nonalcoholic steatohepatitis mice and suppresses hepatic stellate cells activation in CCl4 induced liver fibrosis.
[Nature Communications]
Xu, H., Zhao, Q., Song, N., Yan, Z., Lin, R., Wu, S., Jiang, L., Hong, S., Xie, J., Zhou, H., Wang, R., & Jiang, X. (2020). AdipoR1/AdipoR2 dual agonist recovers nonalcoholic steatohepatitis and related fibrosis via endoplasmic reticulum-mitochondria axis. Nature Communications, 11(1), 5807. https://doi.org/10.1038/s41467-020-19668-y Cite
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Hic-5 Is Required for Activation of Pancreatic Stellate Cells and Development of Pancreatic Fibrosis in Chronic Pancreatitis

Mechanistically, Hic-5 knock down significantly inhibited the TGF-β/Smad2 signaling pathway, resulting in reduced collagen production and α-smooth muscle actin expression in the activated pancreatic stellate cells.
[Scientific Reports]
Gao, L., Lei, X.-F., Miyauchi, A., Noguchi, M., Omoto, T., Haraguchi, S., Miyazaki, T., Miyazaki, A., & Kim-Kaneyama, J. (2020). Hic-5 is required for activation of pancreatic stellate cells and development of pancreatic fibrosis in chronic pancreatitis. Scientific Reports, 10(1), 19105. https://doi.org/10.1038/s41598-020-76095-1 Cite
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MicroRNAs as Regulators, Biomarkers and Therapeutic Targets in Liver Diseases

Investigators review recent advances regarding the regulation and function of miRNAs in liver diseases with a major focus on miRNAs that are specifically expressed or enriched in hepatocytes, neutrophils, hepatic stellate cells, immune cells and in circulation.
[Gut]
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Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-Parenchymal Cell Lineages

Researchers characterized two distinct mesothelial cell types as well as early hepatic stellate cells and revealed distinct spatiotemporal distributions for these populations.
[Cell]
Lotto, J., Drissler, S., Cullum, R., Wei, W., Setty, M., Bell, E. M., Boutet, S. C., Nowotschin, S., Kuo, Y.-Y., Garg, V., Pe’er, D., Church, D. M., Hadjantonakis, A.-K., & Hoodless, P. A. (2020). Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-parenchymal Cell Lineages. Cell, 183(3), 702-716.e14. https://doi.org/10.1016/j.cell.2020.09.012 Cite
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β-Arrestin2 Deficiency Attenuates Oxidative Stress in Mouse Hepatic Fibrosis through Modulation of NOX4

Hepatic fibrosis is a disease characterized by excessive deposition of ECM in the liver. The authors investigated whether β-arrestin2 regulated oxidative stress in hepatic fibrosis.
[Acta Pharmacologica Sinica]
Du, J., Sun, J., Li, N., Li, X., Sun, W., & Wei, W. (2020). β-Arrestin2 deficiency attenuates oxidative stress in mouse hepatic fibrosis through modulation of NOX4. Acta Pharmacologica Sinica, 1–11. https://doi.org/10.1038/s41401-020-00545-9 Cite
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Silencing of Sinusoidal DDR1 Reduces Murine Liver Metastasis by Colon Carcinoma

Liver metastasis depends on the collagenous microenvironment generated by hepatic sinusoidal cells (SCs). Hepatic DDR1 was found to promote C26 liver metastasis and favor the pro-metastatic response of SCs to the tumor.
[Scientific Reports]
Romayor, I., Badiola, I., Benedicto, A., Márquez, J., Herrero, A., Arteta, B., & Olaso, E. (2020). Silencing of sinusoidal DDR1 reduces murine liver metastasis by colon carcinoma. Scientific Reports, 10(1), 18398. https://doi.org/10.1038/s41598-020-75395-w Cite
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