Hippo Signaling in the Liver: Role in Development, Regeneration and Disease

The authors summarize the diverse roles of Hippo signaling in liver biology and highlight areas where outstanding questions remain to be investigated.
[Nature Reviews Gastroenterology & Hepatology]
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Tetramethylpyrazine Prevents Liver Fibrotic Injury in Mice by Targeting Hepatocyte-Derived and Mitochondrial DNA-Enriched Extracellular Vesicles

Researchers investigated whether tetramethylpyrazine exerted liver-protective action through regulating extracellular vesicle-dependent intercellular communication between hepatocytes and hepatic stellate cells.
[Acta Pharmacologica Sinica]
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MAPK p38/Ulk1 Pathway Inhibits Autophagy and Induces IL-1β Expression in Hepatic Stellate Cells

Investigators revealed a continuous signaling pathway, MAPK p38-Ulk1 phosphorylation-Ulk1/Atg13 disruption, which inhibited autophagy and induced IL-1β expression in hepatic stellate cells.
[American Journal of Physiology-Gastrointestinal and Liver Physiology]
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Tenofovir Disoproxil Fumarate Directly Ameliorates Liver Fibrosis by Inducing Hepatic Stellate Cell Apoptosis via Downregulation of PI3K/Akt/mTOR Signaling Pathway

Activated hepatic stellate cell cell lines were used to evaluate the effects of tenofovir disoproxil fumarate and entecavir. After treatment with each antiviral agent, cell viability, morphology, apoptotic features, autophagy and antifibrosis signaling pathways were examined.
[PLoS One]
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MiR-200c-3p Targets SESN1 and Represses the IL-6/AKT Loop to Prevent Cholangiocyte Activation and Cholestatic Liver Fibrosis

Investigators elucidated the role of miR-200c in cholestasis-induced biliary liver fibrosis and cholangiocyte activation, identifying sestrin 1 (SESN1) as a target of miR-200c.
[Laboratory Investigation]
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Matrix Stiffness Modulates Hepatic Stellate Cell Activation into Tumor-Promoting Myofibroblasts via E2F3-Dependent Signaling and Regulates Malignant Progression

Scientists demonstrated that stiffness contributed to mechanosignal transduction in hepatic stellate cells, which promoted hepatocellular carcinoma cells growth and metastasis through secretion of FGF2.
[Cell Death & Disease]
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Berberine Alleviates Liver Fibrosis through Inducing Ferrous Redox to Activate ROS-Mediated Hepatic Stellate Cells Ferroptosis

Researchers investigated the molecular mechanisms underlying the effect of berberine against liver fibrogenesis in thioacetamide and carbon tetrachloride induced mouse liver fibrosis.
[Cell Death Discovery]
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Targeting SYK of Monocyte-Derived Macrophages Regulates Liver Fibrosis via Crosstalking with Erk/Hif1α and Remodeling Liver Inflammatory Environment

Scientists found that inhibition of monocyte-derived macrophages (MoMFs) SYK impaired the expression of CXCL1, reduced the recruitment of inflammatory cells, and promoted the phenotype cross-dress process of pro-resolution MoMFs, thereby remodeling the chronic inflammatory environment of the fibrotic liver.
[Cell Death & Disease]
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Initiation of Hepatic Stellate Cell Activation Extends into Chronic Liver Disease

Scientists identified transcriptional programs of initiating and activated hepatic stellate cells by RNA sequencing, using in vitro and in vivo mouse models of fibrosis.
[Cell Death & Disease]
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Sorafenib Attenuates Liver Fibrosis by Triggering Hepatic Stellate Cell Ferroptosis via HIF-1α/SLC7A11 Pathway

Scientists investigate the functional role of hepatic stellate cell ferroptosis in the anti-fibrotic effect of sorafenib and found that sorafenib attenuated liver injury and extracellular matrix accumulation in CCl4-induced fibrotic livers, accompanied by reduction of SLC7A11 and GPX4 proteins.
[Cell Proliferation]
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Leronlimab (350 mg) Weekly Use for 14 Weeks in Open Label Arm of NASH Trial Produces Fibrosis Reduction as High as 93 Msec amongst First 15 Patients with Average Reduction of 24 Msec

CytoDyn Inc., a late-stage biotechnology company developing leronlimab, a CCR5 antagonist with the potential for multiple therapeutic indications, reported data from its trial treating nonalcoholic steatohepatitis (NASH) open label with leronlimab.
[CytoDyn, Inc.]
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