Journal articleHepatology · February 2, 2026
BACKGROUND AND AIMS: Older age increases susceptibility to metabolic dysfunction-associated steatotic liver disease (MASLD), but whether it impacts response to therapies, and how the therapies impact regulators of biological aging, are poorly understood. S ...
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Journal articleGut · January 13, 2026
BACKGROUND: Why alcohol-associated liver disease (ALD) resolves after abstinence in most people but progresses to liver failure in others remains poorly understood. Experimental models show that increased exposure to proinflammatory cytokines exacerbates A ...
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Journal articleNat Commun · March 28, 2025
Senescent hepatocytes accumulate in metabolic dysfunction-associated steatotic liver disease (MASLD) and are linked to worse clinical outcomes. However, their heterogeneity and lack of specific markers have made them difficult to target therapeutically. He ...
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Journal articleJ Clin Invest · August 27, 2024
The burden of senescent hepatocytes correlates with the severity of metabolic dysfunction-associated steatotic liver disease (MASLD), but the mechanisms driving senescence and how it exacerbates MASLD are poorly understood. Hepatocytes experience lipotoxic ...
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Journal articleNat Aging · July 2024
Susceptibility to the biological consequences of aging varies among organs and individuals. We analyzed hepatocyte transcriptomes of healthy young and aged male mice to generate an aging hepatocyte gene signature, used it to deconvolute transcriptomic data ...
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Journal articleNat Commun · March 4, 2024
Clinical translation of AAV-mediated gene therapy requires preclinical development across different experimental models, often confounded by variable transduction efficiency. Here, we describe a human liver chimeric transgene-free Il2rg-/-/Rag2-/-/Fah-/-/A ...
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Journal articleHepatology · October 1, 2023
BACKGROUND AND AIMS: Senescent hepatocytes accumulate in parallel with fibrosis progression during NASH. The mechanisms that enable progressive expansion of nonreplicating cell populations and the significance of that process in determining NASH outcomes a ...
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Journal articleCell Res · July 2023
Cellular senescence is a stress-induced, stable cell cycle arrest phenotype which generates a pro-inflammatory microenvironment, leading to chronic inflammation and age-associated diseases. Determining the fundamental molecular pathways driving senescence ...
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ConferenceHepatology · June 1, 2023
BACKGROUND AND AIMS: Liver fibrosis results from the accumulation of myofibroblasts (MFs) derived from quiescent HSCs, and yes-associated protein (YAP) controls this state transition. Although fibrosis is also influenced by HSC death and senescence, whethe ...
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ConferenceCell Mol Gastroenterol Hepatol · 2023
BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH), a leading cause of cirrhosis, strongly associates with the metabolic syndrome, an insulin-resistant proinflammatory state that disrupts energy balance and promotes progressive liver degeneration. We a ...
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Journal articleHepatology · October 2022
BACKGROUND AND AIMS: Within the next decade, NAFLD is predicted to become the most prevalent cause of childhood liver failure in developed countries. Predisposition to juvenile NAFLD can be programmed during early life in response to maternal metabolic syn ...
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ConferenceAging Cell · February 2022
Older age is a major risk factor for damage to many tissues, including liver. Aging undermines resiliency and impairs liver regeneration. The mechanisms whereby aging reduces resiliency are poorly understood. Hedgehog is a signaling pathway with critical m ...
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Journal articleiScience · September 24, 2021
Cellular cholesterol is regulated by at least two transcriptional mechanisms involving sterol-regulatory-element-binding proteins (SREBPs) and liver X receptors (LXRs). Although SREBP and LXR pathways are the predominant mechanisms that sense cholesterol i ...
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Journal articleJ Hepatol · September 2021
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD), the hepatic correlate of the metabolic syndrome, is a major risk factor for hepatobiliary cancer (HBC). Although chronic inflammation is thought to be the root cause of all these diseases, the m ...
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Journal articleLiver Int · September 2021
BACKGROUND & AIMS: The outcome of liver injury is dictated by factors that control the accumulation of myofibroblastic (activated) hepatic stellate cells (MF-HSCs) but therapies that specifically block this process have not been discovered. We evaluated th ...
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Journal articleJCI insight · November 2020
Adult liver has enormous regenerative capacity; it can regenerate after losing two-thirds of its mass while sustaining essential metabolic functions. How the liver balances dual demands for increased proliferative activity with maintenance of organ functio ...
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Journal articleAm J Pathol · January 2020
Fibrolamellar carcinoma (FLC) is characterized by in-frame fusion of DnaJ heat shock protein family (Hsp40) member B1 (DNAJB1) with protein kinase cAMP-activated catalytic subunit α (PRKACA) and by dense desmoplasia. Surgery is the only effective treatment ...
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Journal articleBiomaterials · October 2019
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 ...
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Journal articleGut · June 2019
OBJECTIVE: Uncertainty about acute liver failure (ALF) pathogenesis limits therapy. We postulate that ALF results from excessive reactivation of a fetal liver programme that is induced in hepatocytes when acutely injured livers regenerate. To evaluate this ...
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Journal articleJ Hepatol · August 2018
BACKGROUND & AIMS: Chronic failure of mechanisms that promote effective regeneration of dead hepatocytes causes replacement of functional hepatic parenchyma with fibrous scar tissue, ultimately resulting in cirrhosis. Therefore, defining and optimizing mec ...
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Journal articleCell Physiol Biochem · 2018
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 t ...
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Journal articleExp Mol Med · September 22, 2017
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 co ...
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Journal articleLab Invest · May 2017
During progression to type 1 diabetes, insulin-producing β-cells are lost through an autoimmune attack resulting in unrestrained glucagon expression and secretion, activation of glycogenolysis, and escalating hyperglycemia. We recently identified a protein ...
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Journal articleBiomed Mater · November 11, 2016
The in vivo function and phenotype of ovarian follicle cells are determined by many factors. When these cells are removed from the in vivo microenvironment and grown in a 2D in vitro environment, the function of the follicular cells is difficult to preserv ...
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Journal articleClin Mol Hepatol · September 2016
BACKGROUND/AIMS: Chronic liver disease leads to liver fibrosis, and although the liver does have a certain regenerative capacity, this disease is associated with dysfunction of the liver vessels. C-reactive protein (CRP) is produced in the liver and circul ...
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Journal articleAm J Pathol · May 2016
miRNAs are involved in liver regeneration, and their expression is dysregulated in hepatocellular carcinoma (HCC). Connective tissue growth factor (CTGF), a direct target of miR-133b, is crucial in the ductular reaction (DR)/oval cell (OC) response for gen ...
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Journal articleAm J Pathol · June 2015
Hepatic progenitor/oval cell (OC) activation occurs when hepatocyte proliferation is inhibited and is tightly associated with the fibrogenic response during severe liver damage. Connective tissue growth factor (CTGF) is important for OC activation and cont ...
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Journal articleHepatology · February 2015
UNLABELLED: Connective tissue growth factor (CTGF) is a matricellular protein that mediates cell-matrix interaction through various subtypes of integrin receptors. This study investigated the role of CTGF and integrin αvβ6 in hepatic progenitor/oval cell a ...
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Journal articleCell Transplant · 2015
X-linked myotubular myopathy (XLMTM) is an isogenic muscle disease characterized by progressive wasting of skeletal muscle, weakness, and premature death of affected male offspring. Recently, the XLMTM gene knock-in mouse, Mtm1 p.R69C, was found to have a ...
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Journal articleLiver Int · February 2012
BACKGROUND: Somatostatin is a pleiotropic peptide, exerting a variety of effects through its receptor subtypes. Recently, somatostatin has been shown to act as a chemoattractant for haematopoietic progenitor cells and hepatic oval cells (HOC) via receptor ...
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Journal articlePancreas · January 2012
OBJECTIVE: We have identified a novel protein in bone marrow-derived insulin-producing cells. Here we characterize this protein, hereby named islet homeostasis protein (IHoP), in the pancreatic islet. METHODS: Detection of IHoP mRNA and protein was perform ...
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Journal articleOral Surg Oral Med Oral Pathol Oral Radiol Endod · December 2011
OBJECTIVE: The aim of this study was to determine if mesenchymal stem cells (MSCs) could be obtained from mandible marrow aspirates. STUDY DESIGN: In 5 patients, 10 mL marrow aspirates were obtained from both the mandible and the iliac crest. Second passag ...
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Journal articleGut and Liver · September 1, 2011
Background/Aims: In the 2-acetylaminofluorene (2-AAF)/70% partial hepatectomy (PHx) model, the mechanism underlying the differentiation of activated hepatic oval cells (HOCs) into hepatocytes and bile ductile cells is unclear. We investigated the role of c ...
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Journal articleTissue Engineering and Regenerative Medicine · July 1, 2011
Mesenchymal stem cells (MSCs) derived from various human tissues, including amnion (AM) from the placenta and bone marrow (BM), have been known to differentiate into multi-lineages and mesodermal cell lines. Few comparative studies have reported their pote ...
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Journal articleClin Transplant · 2011
Allografts from donors positive for antibody to hepatitis B core antigen (anti-HBc(+)) can transmit hepatitis B virus (HBV) to the recipients. We aimed to study the prevalence of HBV DNA in liver allografts from anti-HBc(+) donors. Between January 2003 and ...
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Journal articleLab Invest · August 2010
Earlier studies conducted by our laboratory have shown that suppression of transforming growth factor-beta (TGFbeta)-mediated upregulation of connective tissue growth factor (CTGF) by iloprost resulted in a greatly diminished oval cell response to 2-acetyl ...
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Journal articleAm J Pathol · June 2010
To date the molecular signals regulating activation, proliferation, and differentiation of hepatic oval cells are not fully understood. The Wnt family is essential in hepatic embryogenesis and implicated in hepatic carcinogenesis. This study elucidates nov ...
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Journal articleJ Clin Invest · November 2009
Arteriovenous malformations (AVMs) are vascular anomalies where arteries and veins are directly connected through a complex, tangled web of abnormal arteries and veins instead of a normal capillary network. AVMs in the brain, lung, and visceral organs, inc ...
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Journal articleOncol Res · 2009
Metaplastic tubular complexes (MTC) have been proposed as precursor lesions for pancreatic adenocarcinoma (PDAC). In this study, we investigated the potential role of bone marrow-derived progenitor cells (BMPC) in the formation of MTC and PDAC in a rat mod ...
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Journal articleMethods Mol Biol · 2009
The pace of research on the potential therapeutic uses of liver stem cells or "oval cells" has accelerated significantly in recent years. Concurrent advancements in techniques for the isolation and characterization of these cells have helped fuel this rese ...
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Journal articleStem Cells Dev · 2009
Adult bone marrow (BM)-derived insulin-producing cells (IPCs) are capable of regulating blood glucose levels in chemically induced hyperglycemic mice. Using cell transplantation therapy, fully functional BM-derived IPCs help to mediate treatment of diabete ...
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Journal articleHepatology International · March 1, 2008
The bone marrow contains stem cells that have the potential to differentiate into a variety of organ-specific mature cells, including the liver and the pancreas. Recently, the origin of hepatic progenitors and hepatocytes was identified to be the bone marr ...
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Journal articleHepatology · March 2008
UNLABELLED: Oval cell activation, as part of the regenerative process after liver injury, involves considerable cell-matrix interaction. The matricellular protein, connective tissue growth factor (CTGF), has been shown to be critical for oval cell activati ...
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Journal articleGastroenterology · August 2007
BACKGROUND AND AIMS: Hepatic regeneration is a heterogeneous phenomenon involving several cell populations. Oval cells are considered liver stem cells, a portion of which derive from bone marrow (BM). Recent studies have shown that granulocyte-colony stimu ...
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Journal articleGastroenterology · March 2007
BACKGROUND AND AIMS: The ability of the bone marrow cells to differentiate into liver, pancreas, and other tissues led to the speculation that these cells might be the source of adult stem cells found in these organs. The present study analyzed whether the ...
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Journal articleAm J Pathol · December 2006
Stromal cell-derived factor-1 (SDF-1) is known to play an essential role in the regulation of stem/progenitor cell trafficking. During hepatic stem, or oval, cell activation, SDF-1 has been reported to be up-regulated within the liver, implying a possible ...
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Journal articleLab Invest · May 2006
Somatostatin (SST) is a regulatory peptide that activates G protein-coupled receptors comprised of five members (somatostatin receptors (SSTRs) 1-5). Despite the broad use of SST and its analogs in clinical practice, the spectrum of SST activities has been ...
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Journal articleGastroenterology · June 2005
BACKGROUND & AIMS: Recruitment and proliferation of Thy-1+ oval cells is a hallmark of liver regeneration after 2-acetylaminofluorene (2-AAF)/partial hepatectomy (PHx) in rats. To understand the molecular mechanism underlying this process, we investigated ...
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Journal articleAm J Pathol · June 2005
Embryonic stem (ES) cells have been proposed to be a powerful tool in the study of pancreatic disease, as well as a potential source for cell replacement therapy in the treatment of diabetes. However, data demonstrating the feasibility of using pancreatic ...
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Journal articleJ Hepatobiliary Pancreat Surg · 2005
The transplantation of pancreatic beta cells or hepatocytes represents a potential therapeutic approach for type I diabetes and inherited liver diseases, respectively. Furthermore, acquired liver diseases, particularly acute hepatic failure due to toxic or ...
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Journal articleLab Invest · May 2004
Recent findings suggest that bone marrow (BM) cells have the capacity to differentiate into a variety of cell types including endocrine cells of the pancreas. We report that BM derived cells, when cultured under defined conditions, were induced to trans-di ...
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Journal articleSemin Cell Dev Biol · December 2002
Hepatic oval cell activation, proliferation, and differentiation has been observed under certain physiological conditions, mainly when the proliferation of existing hepatocytes has been inhibited followed by severe hepatic injury. Hepatic oval cells displa ...
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Journal articleBiochem Biophys Res Commun · December 20, 2000
Bone marrow (BM) cells originally include alpha-fetoprotein (AFP)- and c-Met [a receptor for hepatocyte growth factor (HGF)]-expressing cells. In vitro treatment of BM cells with HGF induced albumin-expressing hepatocyte-like cells. Furthermore, those hepa ...
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