A5042170885- Liver Disease Diagnosis and Treatment
- Liver physiology and pathology
- Liver Disease and Transplantation
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Organ Transplantation Techniques and Outcomes
- Pediatric Hepatobiliary Diseases and Treatments
- Peptidase Inhibition and Analysis
- Hepatocellular Carcinoma Treatment and Prognosis
- Liver Diseases and Immunity
- Bone Metabolism and Diseases
- Endoplasmic Reticulum Stress and Disease
- Immune Cell Function and Interaction
- Pancreatic function and diabetes
- Hepatitis C virus research
- Cancer-related molecular mechanisms research
- Bone health and treatments
- Drug-Induced Hepatotoxicity and Protection
- CAR-T cell therapy research
- Cancer, Hypoxia, and Metabolism
- Galectins and Cancer Biology
- Drug Transport and Resistance Mechanisms
- NF-κB Signaling Pathways
- Protease and Inhibitor Mechanisms
- Pancreatic and Hepatic Oncology Research
- Wnt/β-catenin signaling in development and cancer
Doshisha University
2018-2025
Kyoto University
2015-2025
Osaka University
2021-2025
Life Systems (United States)
2021
University of California, San Diego
2009-2020
657 Oslo
2016
National Agriculture and Food Research Organization
2015
Food Research Institute
2015
Keio University
2015
Aichi Medical University
2015
Myofibroblasts produce the fibrous scar in hepatic fibrosis. In carbon tetrachloride (CCl(4)) model of liver fibrosis, quiescent stellate cells (HSC) are activated to become myofibroblasts. When underlying etiological agent is removed, clinical and experimental fibrosis undergoes a remarkable regression with complete disappearance these Although some myofibroblasts apoptose, it unknown whether other may revert an inactive phenotype during We elucidated fate HSCs/myofibroblasts recovery from...
Significance Liver resident activated hepatic stellate cells (aHSCs), and portal fibroblasts (aPFs) are the major source of fibrous scar in liver. aPFs have been implicated liver fibrosis caused by cholestatic injury, whereas hepatotoxic injury is attributed to aHSCs. However, contribution not well characterized because difficulties cell purification lack identified aPF-specific markers. We developed a novel flow cytometry-based method from nonparenchymal fraction collagen-α1(I)-GFP mice...
Impairment of the circadian clock has been associated with numerous disorders, including metabolic disease. Although small molecules that modulate function might offer therapeutic approaches to such diseases, only a few compounds have identified selectively target core proteins. From an unbiased cell-based phenotypic screen, we KL001, molecule specifically interacts cryptochrome (CRY). KL001 prevented ubiquitin-dependent degradation CRY, resulting in lengthening period. In combination...
The origin of fibrogenic cells in liver fibrosis remains controversial. We assessed the emerging concept that hepatocytes contribute to production extracellular matrix (ECM) through epithelial-mesenchymal transition (EMT). bred triple transgenic mice expressing ROSA26 stop β-galactosidase (β-gal), albumin Cre, and collagen α1(I) green fluorescent protein (GFP), which hepatocyte-derived are permanently labeled by β-gal type I collagen-expressing GFP. induced repetitive carbon tetrachloride...
CCAAT/enhancer-binding protein (C/EBP) homologous (CHOP) is a key component in endoplasmic reticulum (ER) stress-mediated apoptosis. The goal of the study was to investigate role CHOP cholestatic liver injury. Acute injury and fibrosis were assessed wild-type (WT) CHOP-deficient mice following bile duct ligation (BDL). In WT livers, BDL induced overexpression Bax, downstream target CHOP-mediated ER stress pathway. Liver attenuated CHOP-knockout mice. Expression levels alpha-smooth muscle...
Abstract Purpose: To investigate the diagnostic value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) for prediction tumor differentiation, P-glycoprotein (P-gp) expression, and outcome in hepatocellular carcinoma (HCC) patients. Experimental Design: Seventy HCC patients who underwent curative resection were prospectively enrolled study. FDG-PET was done 2 weeks preoperatively, standardized uptake (SUV) to nontumor SUV ratio (TNR) calculated from FDG uptake. Tumor...
Abstract Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is a multicomponent enzyme that mediates electron transfer from nicotinamide to molecular oxygen, which leads the production of superoxide. NOX2/gp91phox catalytic subunit NOX expressed in phagocytic cells. Several homologues NOX2, including NOX1, have been identified nonphagocytic We investigated contributory role NOX1 and NOX2 hepatic fibrosis. Hepatic fibrosis was induced wild-type (WT) mice, knockout (NOX1KO) (NOX2KO)...
Excessive acetaminophen (APAP) use is one of the most common causes acute liver failure. Various types cell death in damaged are linked to APAP-induced hepatotoxicity, and, these, necrotic hepatocytes has been shown be involved disease pathogenesis. Until recently, necrosis was commonly considered a random and unregulated form death; however, recent studies have identified previously unknown programmed called receptor-interacting protein kinase (RIPK)-dependent (or necroptosis), which...
Peroxisome proliferator-activated receptor delta (PPARδ), a member of the nuclear family, is emerging as key metabolic regulator with pleiotropic actions on various tissues including fat, skeletal muscle, and liver. Here we show that PPARδ agonist KD3010, but not well-validated GW501516, dramatically ameliorates liver injury induced by carbon tetrachloride (CCl 4 ) injections. Deposition extracellular matrix proteins was lower in KD3010-treated group than vehicle- or GW501516-treated group....
Most chronic liver diseases of all etiologies result in progressive fibrosis. Myofibroblasts produce the extracellular matrix, including type I collagen, which constitutes fibrous scar Normal has little collagen and no detectable myofibroblasts, but myofibroblasts appear early experimental clinical injury. The origin myofibroblast fibrosis is still unresolved. possibilities include activation endogenous mesenchymal cells fibroblasts hepatic stellate cells, recruitment from bone marrow,...
Abstract Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are liver originated malignant tumors. Of the two, ICC has worse prognosis because it no reliable diagnostic markers its carcinogenic mechanism is not fully understood. The aim of this study was to integrate metabolomics transcriptomics datasets identify variances if any in HCC. Ten 6 HCC who were resected surgically, enrolled. miRNA mRNA expression analysis performed by microarray on their corresponding...
Cholestatic liver fibrosis is caused by obstruction of the biliary tract and associated with early activation portal fibroblasts (PFs) that express Thy-1, fibulin 2, recently identified marker mesothelin (MSLN). Here, we have demonstrated activated PFs (aPFs) myofibroblasts play a critical role in pathogenesis induced bile duct ligation (BDL). Conditional ablation MSLN+ aPFs BDL-injured mice attenuated approximately 50%. Similar results were observed MSLN-deficient (Msln-/- mice) or...
This report addresses whether small molecules can deplete FoxP3-expressing regulatory T (T reg) cells, thereby augmenting antitumor immunity. Imatinib, a tyrosine kinase inhibitor of oncogenic BCR-ABL protein expressed by chronic myelogenous leukemia (CML) possesses off-targets including LCK in cells. We showed that imatinib-treated CML patients complete molecular remission (CMR) exhibited selective depletion effector reg (eT cells and significant increase effector/memory CD8+ while non-CMR...
Liver fibrosis is the result of entire organism responding to a chronic injury. Every cell type in liver contributes fibrosis. This paper first discusses key intracellular signaling pathways that are induced during The then examines effects these on major types liver. will provide insights into molecular pathophysiology and should identify therapeutic targets.
Hepatic stellate cells (HSCs) constitute the liver sinusoid with Kupffer and sinusoidal endothelial cells. While functions as gateway to inflammation, whether HSCs contribute inflammation and, if so, how they exert such remain elusive. Here, we found that mouse well human expressed DP1 receptor for prostaglandin D 2 selectively in liver. Pharmacological stimulation of by BW245C, a DP1‐selective agonist, suppressed activation cultured tumor necrosis factor‐α at least part through...