Targeted Deletion of Thymosin Beta 4 in Hepatic Stellate Cells Ameliorates Liver Fibrosis in a Transgenic Mouse Model.

Liver fibrosis is the most common feature of liver disease, and activated hepatic stellate cells (HSCs) are the main contributors to liver fibrosis. Thus, finding key targets that modulate HSC activation is important to prevent liver fibrosis. Previously, we showed that thymosin β4 (Tβ4) influenced HSC activation by interacting with the Hedgehog pathway in vitro.

sEVs from tonsil-derived mesenchymal stromal cells alleviate activation of hepatic stellate cells and liver fibrosis through miR-486-5p.

Mesenchymal stromal cells (MSCs) are considered as a promising therapeutic tool for liver fibrosis, a main feature of chronic liver disease. Because small extracellular vesicles (sEVs) harboring a variety of proteins and RNAs are known to have similar functions with their derived cells, MSC-derived sEVs carry out the regenerative capacities of MSCs. Human tonsil-derived MSCs (T-MSCs) are reported as a novel source of MSCs, but their effects on liver fibrosis remain unclear.

Ubiquitination of PPAR-gamma by pVHL inhibits ACLY expression and lipid metabolism, is implicated in tumor progression.

Background: Intracellular lipid accumulation is associated with various diseases, particularly cancer. Mitochondrial dysfunction is considered as a cause of lipid accumulation; however, the related underlying mechanism remains unclear.

Findings: We found that Von Hippel-Lindau (VHL)-deficiency led to lipid accumulation and mitochondrial dysfunction in renal cell carcinoma cells.

Tumor necrosis factor-inducible gene 6 interacts with CD44, which is involved in fate-change of hepatic stellate cells.

Tumor necrosis factor-inducible gene 6 protein (TSG-6) is a cytokine secreted by mesenchymal stem cells (MSCs) and regulates MSC stemness. We previously reported that TSG-6 changes primary human hepatic stellate cells (pHSCs) into stem-like cells by activating yes-associated protein-1 (YAP-1). However, the molecular mechanism behind the reprogramming action of TSG-6 in pHSCs remains unknown.

Tumor necrosis factor-inducible gene 6 reprograms hepatic stellate cells into stem-like cells, which ameliorates liver damage in mouse.

Liver fibrosis is a major characteristic of liver disease. When the liver is damaged, quiescent hepatic stellate cells (HSCs) transdifferentiate into proliferative myofibroblastic/activated HSCs, which are the main contributors to liver fibrosis. Hence, a strategy for regulating HSC activation is important in the treatment of liver disease.

Hepatoprotective Effect of Kombucha Tea in Rodent Model of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis.

Kombucha tea (KT) has emerged as a substance that protects the liver from damage; however, its mechanisms of action on the fatty liver remain unclear. Therefore, we investigated the potential role of KT and its underlying mechanisms on nonalcoholic fatty liver disease (NAFLD). / mice that were fed methionine/choline-deficient (MCD) diets for seven weeks were treated for vehicle (M + V) or KT (M + K) and fed with MCD for four additional weeks.

Effect of Kombucha on gut-microbiota in mouse having non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disorders. Possible links have been recently found between the gut-microbiota and the host metabolism in development of NAFLD and obesity. Therefore, understanding the changes in intestinal microbiota during the progression of NAFLD, is important.

Blood-Stage Plasmodium Berghei ANKA Infection Promotes Hepatic Fibrosis by Enhancing Hedgehog Signaling in Mice.

Background/aims: Malaria is the most deadly parasitic infection in the world, resulting in damage to various organs, including the liver, of the infected organism; however, the mechanism causing this damage in the liver remains unclear. Liver fibrosis, a major characteristic of liver diseases, occurs in response to liver injury and is regulated by a complex network of signaling pathways. Hedgehog (Hh) signaling orchestrates a number of hepatic responses including hepatic fibrogenesis.

RNA Binding Proteins Control Transdifferentiation of Hepatic Stellate Cells into Myofibroblasts.

Background/aims: Myofibroblasts (MF) derived from quiescent nonfibrogenic hepatic stellate cells (HSC) are the major sources of fibrous matrix in cirrhosis. Because many factors interact to regulate expansion and regression of MF-HSC populations, efforts to prevent cirrhosis by targeting any one factor have had limited success, motivating research to identify mechanisms that integrate these diverse inputs. As key components of RNA regulons, RNA binding proteins (RBPs) may fulfill this function by orchestrating changes in the expression of multiple genes that must be coordinately regulated to affect the complex phenotypic modifications required for HSC transdifferentiation.

MicroRNA-378 is involved in hedgehog-driven epithelial-to-mesenchymal transition in hepatocytes of regenerating liver.

Healthy livers have a remarkable regenerative capacity for reconstructing functional hepatic parenchyma after 70% partial hepatectomy (PH). Hepatocytes, usually quiescent in normal healthy livers, proliferate to compensate for hepatic loss after PH. However, the mechanism of hepatocyte involvement in liver regeneration remains unclear.

Tumor necrosis factor-inducible gene 6 protein ameliorates chronic liver damage by promoting autophagy formation in mice.

Tumor necrosis factor-inducible gene 6 protein (TSG-6) has recently been shown to protect the liver from acute damage. However, the mechanism underlying the effect of TSG-6 on the liver remains unclear. Autophagy is a catabolic process that targets cell components to lysosomes for degradation, and its functions are reported to be dysregulated in liver diseases.

Thymosin beta-4 regulates activation of hepatic stellate cells via hedgehog signaling.

The molecular mechanisms of thymosin beta-4 (TB4) involved in regulating hepatic stellate cell (HSC) functions remain unclear. Therefore, we hypothesize that TB4 influences HSC activation through hedgehog (Hh) pathway. HSC functions declined in a TB4 siRNA-treated LX-2.

Hedgehog Signaling is Associated with Liver Response to Fractionated Irradiation in Mice.

Background/aims: Radiation-induced liver disease (RILD) is a major obstacle in treating liver cancer; however, the mechanisms underlying RILD development remain unclear. Hedgehog (Hh) orchestrates liver response to injury. Herein, we investigated the liver response with Hh to fractionated irradiation (FI) using a small murine model for RILD.

Kombucha tea prevents obese mice from developing hepatic steatosis and liver damage.

Nonalcoholic fatty liver disease (NAFLD) is associated with the increased accumulation of hepatocellular lipids. Although Kombucha tea (KT) has emerged as a substance protecting the liver from damage, the effects of KT in NAFLD remain unclear. Hence, we investigated whether KT influenced hepatic steatosis.

MicroRNA Expression Profiling in CCl₄-Induced Liver Fibrosis of Mus musculus.

Liver fibrosis is a major pathological feature of chronic liver diseases, including liver cancer. MicroRNAs (miRNAs), small noncoding RNAs, regulate gene expression posttranscriptionally and play important roles in various kinds of diseases; however, miRNA-associated hepatic fibrogenesis and its acting mechanisms are poorly investigated. Therefore, we performed an miRNA microarray in the fibrotic livers of Mus musculus treated with carbon-tetrachloride (CCl₄) and analyzed the biological functions engaged by the target genes of differentially-expressed miRNAs through gene ontology (GO) and in-depth pathway enrichment analysis.

MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression.

Hedgehog (Hh) signalling regulates hepatic fibrogenesis. MicroRNAs (miRNAs) mediate various cellular processes; however, their role in liver fibrosis is unclear. Here we investigate regulation of miRNAs in chronically damaged fibrotic liver.

MicroRNA125b-mediated Hedgehog signaling influences liver regeneration by chorionic plate-derived mesenchymal stem cells.

Although chorionic plate-derived mesenchymal stem cells (CP-MSCs) were shown to promote liver regeneration, the mechanisms underlying the effect remain unclear. Hedgehog (Hh) signaling orchestrates tissue reconstruction in damaged liver. MSCs release microRNAs mediating various cellular responses.

Tumor necrosis factor-inducible gene 6 promotes liver regeneration in mice with acute liver injury.

Introduction: Tumor necrosis factor-inducible gene 6 protein (TSG-6), one of the cytokines released by human mesenchymal stem/stromal cells (hMSC), has an anti-inflammatory effect and alleviates several pathological conditions; however, the hepatoprotective potential of TSG-6 remains unclear. We investigated whether TSG-6 promoted liver regeneration in acute liver failure.

Methods: The immortalized hMSC (B10) constitutively over-expressing TSG-6 or empty plasmid (NC: Negative Control) were established, and either TSG-6 or NC-conditioned medium (CM) was intraperitoneally injected into mice with acute liver damage caused by CCl4.

Hepatic stellate cells express thymosin Beta 4 in chronically damaged liver.

Although the various biological roles of thymosin β4 (Tβ4) have been studied widely, the effect of Tβ4 and Tβ4-expressing cells in the liver remains unclear. Therefore, we investigated the expression and function of Tβ4 in chronically damaged livers. CCl4 was injected into male mice to induce a model of chronic liver disease.

Hedgehog signaling influences gender-specific response of liver to radiation in mice.

Background: It is unclear why the response to radiation in the female liver is different from that of the male liver. Hedgehog (Hh) that remains latent in healthy adult livers is activated in the injured liver and promotes the proliferation of progenitors and myofibroblastic hepatic stellate cells, leading to hepatic fibrosis.

Objective: These findings have led to the hypothesis that the gender-specific expression of Hh signaling could affect the different response of the female liver to radiation.

Potential role of Hedgehog pathway in liver response to radiation.

Radiation-induced fibrosis constitutes a major problem that is commonly observed in the patients undergoing radiotherapy; therefore, understanding its pathophysiological mechanism is important. The Hedgehog (Hh) pathway induces the proliferation of progenitors and myofibroblastic hepatic stellate cells (MF-HSCs) and promotes the epithelial-to-mesenchymal transition (EMT), thereby regulating the repair response in the damaged liver. We examined the response of normal liver to radiation injury.

Hedgehog signaling regulates the repair response in mouse liver damaged by irradiation.

Radiotherapy is commonly used in treating many kinds of cancers that cannot be cured by other therapeutic strategies. However, radiation-induced fibrosis in the treatment of intrahepatic cancer is a major obstacle. Hedgehog pathway is known to regulate the fibrotic process and proliferation of progenitor cells.