Novel Insights into Liver Homeostasis and Regeneration

Three important new studies explore liver regeneration and homeostasis using novel lineage tagging of hepatic cells and single-cell RNA transcriptomics.
[Nature Reviews Gastroenterology & Hepatology]
Michalopoulos, G. K. (2021). Novel insights into liver homeostasis and regeneration. Nature Reviews Gastroenterology & Hepatology, 1–2. https://doi.org/10.1038/s41575-021-00454-0 Cite
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Microvesicles Derived from Human Umbilical Cord Mesenchyme Promote M2 Macrophage Polarization and Ameliorate Renal Fibrosis Following Partial Nephrectomy via Hepatocyte Growth Factor

Scientists investigated whether icrovesicles derived from human Wharton’s Jelly mesenchymal stromal cells regulated macrophage polarization and ameliorated renal fibrosis following ischemia-PN via transferring hepatocyte growth factor.
[Human Cell]
Du, T., Ju, G., Zhou, J., Zhong, L., Rong, L., Chen, W., Zhang, X., Zhou, R., Ding, D., & Ji, T. (2021). Microvesicles derived from human umbilical cord mesenchyme promote M2 macrophage polarization and ameliorate renal fibrosis following partial nephrectomy via hepatocyte growth factor. Human Cell. https://doi.org/10.1007/s13577-021-00525-z Cite
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Tumor Restriction by Type I Collagen Opposes Tumor-Promoting Effects of Cancer-Associated Fibroblasts

Cancer-associated fibroblasts (CAFs) may exert tumor-promoting and tumor-suppressive functions, but the mechanisms underlying these opposing effects remain elusive. The authors sought to understand these potentially opposing functions by interrogating functional relationships between CAF subtypes, their mediators, desmoplasia and tumor growth in a wide range of tumor types metastasizing to the liver, the most common organ site for metastasis.
[Journal of Clinical Investigation]
Bhattacharjee, S., Hamberger, F., Ravichandra, A., Miller, M., Nair, A., Affo, S., Filliol, A., Chin, L., Savage, T. M., Yin, D., Wirsik, N. M., Mehal, A., Arpaia, N., Seki, E., Mack, M., Zhu, D., Sims, P. A., Stanger, B. Z., Olive, K. P., … Schwabe, R. F. (2021). Tumor restriction by type I collagen opposes tumor-promoting effects of cancer-associated fibroblasts. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI146987 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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Hepatic Differentiation of Human Embryonic Stem Cells by Coupling Substrate Stiffness and Microtopography

Four topographical configurations on stiff or soft polyacrylamide hydrogel were combined to direct hepatic differentiation of human H1 cells via a four-stage protocol, and the coupled impacts of stiffness and topography were quantified at distinct stages.
[Biomaterials Science]
Luo, C., Lü, D., Zheng, L., Zhang, F., Zhang, X., Lü, S., Zhang, C., Jia, X., Shu, X., Li, P., Li, Z., & Long, M. (2021). Hepatic differentiation of human embryonic stem cells by coupling substrate stiffness and microtopography. Biomaterials Science. https://doi.org/10.1039/D1BM00174D 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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Hepatic Differentiation of Human Embryonic Stem Cells by Coupling Substrate Stiffness and Microtopography

Researchers implied that the coupling of substrate stiffness and topography, combined with the biochemical signals, was favorable to improve the efficiency and functionality of hepatic differentiation of human ESCs.
[Biomaterials Science]
Luo, C., Lü, D., Zheng, L., Zhang, F., Zhang, X., Lü, S., Zhang, C., Jia, X., Shu, X., Li, P., Li, Z., & Long, M. (2021). Hepatic differentiation of human embryonic stem cells by coupling substrate stiffness and microtopography. Biomaterials Science. https://doi.org/10.1039/D1BM00174D 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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Metformin Regulates the Th17/Treg Balance by Glycolysis with TIGAR in Hepatic Ischemia-Reperfusion Injury

The I/R liver injury rat model and the primary hepatocyte hypoxia/reoxygenation injury model were established. The biochemical indexes, inflammatory factor indexes, Th17/Treg balance and energy metabolism were evaluated.
[Journal of Pharmacological Sciences]
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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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