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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Functional Characterization of Organoids Derived from Irreversibly Damaged NASH Patient Liver

After hepatic differentiation, NASH liver organoids exhibited reduced ability to dedifferentiate back to the biliary state, consistent with the known reduced regenerative ability of NASH livers.
[Hepatology]
McCarron, S., Bathon, B., Conlon, D. M., Abbey, D., Rader, D. J., Gawronski, K., Brown, C. D., Olthoff, K. M., Shaked, A., & Raabe, T. D. (n.d.). Functional characterization of organoids derived from irreversibly damaged NASH patient liver. Hepatology, n/a(n/a). https://doi.org/https://doi.org/10.1002/hep.31857 Cite
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Chitinase 3-Like 1 Is a Profibrogenic Factor Overexpressed in the Aging Liver and in Patients with Liver Cirrhosis

Scientists hypothesized that the pace of fibrosis progression might reflect changes in gene expression within the aging liver.
[Proceedings of the National Academy of Sciences of the United States of America]
Nishimura, N., Battista, D. D., McGivern, D. R., Engle, R. E., Tice, A., Fares-Gusmao, R., Kabat, J., Pomerenke, A., Nguyen, H., Sato, S., Bock, K. W., Moore, I. N., Kleiner, D. E., Zamboni, F., Alter, H. J., Govindarajan, S., & Farci, P. (2021). Chitinase 3-like 1 is a profibrogenic factor overexpressed in the aging liver and in patients with liver cirrhosis. Proceedings of the National Academy of Sciences, 118(17). https://doi.org/10.1073/pnas.2019633118 Cite
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Cholesterol-binding Translocator Protein TSPO Regulates Steatosis and Bile Acid Synthesis in Non-Alcoholic Fatty Liver Disease

Loss of translocator protein in hepatocytes in vitro downregulated acetyl-CoA acetyltransferase 2 and increased free cholesterol.
[iScience]
Li, Y., Chen, L., Li, L., Sottas, C., Petrillo, S. K., Lazaris, A., Metrakos, P., Wu, H., Ishida, Y., Saito, T., Golden-Mason, L., Rosen, H. R., Wolff, J. J., Silvescu, C. I., Garza, S., Cheung, G., Huang, T., Fan, J., Culty, M., … Papadopoulos, V. (2021). Cholesterol-binding Translocator Protein TSPO Regulates Steatosis and Bile Acid Synthesis in Non-Alcoholic Fatty Liver Disease. IScience, 0(0). https://doi.org/10.1016/j.isci.2021.102457 Cite
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Integrin αVβ1 Regulates Procollagen I Production through a Non-canonical Transforming Growth Factor β Signaling Pathway in Human Hepatic Stellate Cells

Based on mRNA and protein expression profiling data, investigators found that αVβ1 integrin is the most abundant member of the αV integrin family in either quiescent or transforming growth factor β (TGF-β)1-activated primary human hepatic stellate cells.
[Biochemical Journal]
Han, Z., Ma, Y., Cao, G., Ma, Z., Chen, R., Cvijic, M. E., & Cheng, D. (2021). Integrin αVβ1 Regulates Procollagen I Production through a Non-canonical Transforming Growth Factor β Signaling Pathway in Human Hepatic Stellate Cells. Biochemical Journal, BCJ20200749. https://doi.org/10.1042/BCJ20200749 Cite
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Directed Differentiation of Human Induced Pluripotent Stem Cells to Hepatic Stellate Cells

Researchers describe a protocol to differentiate human induced pluripotent stem cells into hepatic stellate cells.
[Nature Protocols]
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Co-encapsulation of Collagenase Type I and Silibinin in Chondroitin Sulfate Coated Multilayered Nanoparticles for Targeted Treatment of Liver Fibrosis

Investigators demonstrated that chondroitin sulfate coated multilayered 50-nm nanoparticles encapsulating collagenase and silibinin broke down the dense collagen stroma, while silibinin inhibited activated hepatic stellate cells.
[Carbohydrate Polymers]
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Bmal1 Inhibits Phenotypic Transformation of Hepatic Stellate Cells in Liver Fibrosis via IDH1/α-KG-Mediated Glycolysis

Scientists showed that glycolysis was significantly enhanced, while the expression of brain and muscle arnt-like protein-1 (Bmal1) was downregulated in fibrotic liver tissues of mice, primary Hepatic stellate cells (HSCs), and transforming growth factor-β1 (TGF-β1)-induced LX2 cells.
[Acta Pharmaceutica Sinica B]
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Exosome-Delivered CD44v6/C1QBP Complex Drives Pancreatic Cancer Liver Metastasis by Promoting Fibrotic Liver Microenvironment

Researchers explored the underlying mechanisms of how pancreatic ductal adenocarcinoma-derived exosomes modulate the liver microenvironment and promote metastasis.
[Pancreas]
Xie, Z., Gao, Y., Ho, C., Li, L., Jin, C., Wang, X., Zou, C., Mao, Y., Wang, X., Li, Q., Fu, D., & Zhang, Y.-F. (2021). Exosome-delivered CD44v6/C1QBP complex drives pancreatic cancer liver metastasis by promoting fibrotic liver microenvironment. Gut. https://doi.org/10.1136/gutjnl-2020-323014 Cite
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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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The Effect of Bone Marrow-Derived Mesenchymal Stem Cell Co-Transplantation with Hematopoietic Stem Cells on Liver Fibrosis Alleviation and Survival in Patients with Class III β-Thalassemia Major

The authors evaluated the effect of co-transplantation of bone marrow-derived MSC with HSCs on the liver fibrosis alleviation and transplant outcomes in class III beta-thalassemia major.
[Stem Cell Research & Therapy]
Rostami, T., Kasaeian, A., Maleki, N., Nikbakht, M., Kiumarsi, A., Tavangar, S. M., Taheri, A. P. H., Mousavi, S. A., & Ghavamzadeh, A. (2021). The effect of bone marrow-derived mesenchymal stem cell co-transplantation with hematopoietic stem cells on liver fibrosis alleviation and survival in patients with class III β-thalassemia major. Stem Cell Research & Therapy, 12(1), 213. https://doi.org/10.1186/s13287-021-02242-8 Cite
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