Small Extracellular Vesicles Derived from Interferon-γ Pre-Conditioned Mesenchymal Stromal Cells Effectively Treat Liver Fibrosis

Investigators analyzed the therapeutic potential of small extracellular vesicles (sEVs) derived from interferon-γ (IFN-γ) pre-conditioned MSCs (γ-sEVs).
[NPJ Regenerative Medicine]
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N-n-Butyl Haloperidol Iodide Ameliorates Liver Fibrosis and Hepatic Stellate Cell Activation in Mice

Researchers revealed that c-Jun was bound to the TGF-β receptor II (TGFBR2) promoter, whereas N-n-Butyl haloperidol iodide suppressed the binding of c-Jun to the TGFBR2 promoter to restrain TGF-β signaling and inhibit α-smooth muscle actin and collagen I upregulation.
[Acta Pharmacologica Sinica]
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Hepatic Stellate Cells Promote Intrahepatic Cholangiocarcinoma Progression via NR4A2/osteopontin/Wnt Signaling Axis

By establishing co-culture models of Intrahepatic cholangiocarcinoma (ICC) cells and hepatic stellate cells (HSCs), researchers identified that HSCs triggered the expression of nuclear receptor family 4 subgroup A member 2 (NR4A2), a transcription factor previously reported as a molecular switch between inflammation and cancer, in ICC cells.
[Oncogene]
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Gli2-Regulated Activation of Hepatic Stellate Cells and Liver Fibrosis by TGF-β Signaling

Scientists investigated the effect of Gli2 on liver fibrogenesis and its possible mechanism using conditional knockout Gli2 mice and hepatic stellate cell models.
[American Journal of Physiology-Gastrointestinal and Liver Physiology]
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Genevant Sciences Announces Global Collaboration and License Agreement with Takeda to Develop Novel Nucleic Acid Therapeutics for Liver Fibrosis

Genevant Sciences, announced that it has entered into a global collaboration and license agreement with Takeda Pharmaceutical Company Limited for the discovery, development and commercialization of LNP-delivered nucleic acid therapeutics directed to previously inaccessible drug targets in hepatic stellate cells to treat liver fibrosis.
[Genevant Sciences]
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Inhibition of miR‐188‐5p Alleviates Hepatic Fibrosis by Significantly Reducing the Activation and Proliferation of HSCs through PTEN/PI3K/AKT Pathway

Mimicking the miR‐188‐5p resulted in the up‐regulation of hepatic stellate cell (HSC) activation and proliferation by directly targeting the phosphatase and tensin homolog (PTEN). Inhibition of miR‐188‐5p reduced the activation and proliferation markers of HSCs through PTEN/AKT pathway.
[Journal of Cellular and Molecular Medicine]
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Proliferation Tracing Reveals Regional Hepatocyte Generation in Liver Homeostasis and Repair

Cell proliferation tracing revealed that, at the whole hepatocyte–population level, more proliferation was detected in a subset of midzonal hepatocytes during liver homeostasis, with less proliferation in periportal hepatocytes and minimal proliferation in pericentral hepatocytes.
[Science]
He, L., Pu, W., Liu, X., Zhang, Z., Han, M., Li, Y., Huang, X., Han, X., Li, Y., Liu, K., Shi, M., Lai, L., Sun, R., Wang, Q.-D., Ji, Y., Tchorz, J. S., & Zhou, B. (2021). Proliferation tracing reveals regional hepatocyte generation in liver homeostasis and repair. Science, 371(6532). https://doi.org/10.1126/science.abc4346 Cite
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Dynamically Remodeled Hepatic Extracellular Matrix Predicts Prognosis of Early-Stage Cirrhosis

Investigators systematically analyzed proteomics of decellularized hepatic matrix and identified four unique clusters of ECM proteins at tissue damage/inflammation, transitional ECM remodeling or fibrogenesis stage in carbon tetrachloride-induced liver fibrosis.
[Cell Death & Disease]
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Heterogeneity of Hepatic Stellate Cells in a Mouse Model of Non-Alcoholic Steatohepatitis (NASH)

Researchers examined the single cell expression profiles of hepatic stellate cells purified from the normal livers of foz/foz mice on a chow diet, in NASH with fibrosis of foz/foz mice on a Western diet, and in livers during regression of non‐alcoholic steatohepatitis after switching back to a chow diet.
[Hepatology]
Rosenthal, S. B., Liu, X., Ganguly, S., Dhar, D., Pasillas, M. P., Ricciardelli, E., Li, R. Z., Troutman, T. D., Kisseleva, T., Glass, C. K., & Brenner, D. A. (n.d.). Heterogeneity of hepatic stellate cells in a mouse model of non-alcoholic steatohepatitis (NASH). Hepatology, n/a(n/a). https://doi.org/https://doi.org/10.1002/hep.31743 Cite
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Hepatic Macrophages Act as a Central Hub for Relaxin-Mediated Alleviation of Liver Fibrosis

Researchers showed that hepatic macrophages expressed the primary relaxin receptor, and that, on relaxin binding, they switch from the profibrogenic to the pro-resolution phenotype.
[Nature Nanotechnology]
Hu, M., Wang, Y., Liu, Z., Yu, Z., Guan, K., Liu, M., Wang, M., Tan, J., & Huang, L. (2021). Hepatic macrophages act as a central hub for relaxin-mediated alleviation of liver fibrosis. Nature Nanotechnology, 1–12. https://doi.org/10.1038/s41565-020-00836-6 Cite
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Targeting Transdifferentiated Hepatic Stellate Cells and Monitoring the Hepatic Fibrogenic Process by Means of IGF2R-Specific Peptides Designed In Silico

The structural information of the insulin-like growth factor 2 receptor (IGF2R), an overexpressed protein on activated hepatic stellate cells, were used for an in silico screening of novel IGF2R-specific peptide ligands.
[Journal of Materials Chemistry B]
Weber, F., Casalini, T., Valentino, G., Brülisauer, L., Andreas, N., Koeberle, A., Kamradt, T., Contini, A., & Luciani, P. (2021). Targeting transdifferentiated hepatic stellate cells and monitoring the hepatic fibrogenic process by means of IGF2R-specific peptides designed in silico. Journal of Materials Chemistry B. https://doi.org/10.1039/D0TB02372H Cite
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