In Vivo Hepatic Reprogramming of Myofibroblasts with AAV Vectors as a Therapeutic Strategy for Liver Fibrosis.
Cell Stem Cell 18(6):809 (2016)
Liver fibrosis, a form of scarring, develops in chronic liver diseases when hepatocyte regeneration cannot compensate for hepatocyte death. Initially, collagen produced by myofibroblasts (MFs) functions to maintain the integrity of the liver, but excessive collagen accumulation suppresses residu...
Direct Reprogramming of Hepatic Myofibroblasts into Hepatocytes In Vivo Attenuates Liver Fibrosis.
Cell Stem Cell 18(6):797 (2016)
Direct induction of induced hepatocytes (iHeps) from fibroblasts holds potential as a strategy for regenerative medicine but until now has only been shown in culture settings. Here, we describe in vivo iHep formation using transcription factor induction and genetic fate tracing in mouse models o...
Epithelial Transforming Growth Factor-β Signaling Does Not Contribute to Liver Fibrosis but Protects Mice From Cholangiocarcinoma.
Gastroenterology 150(3):720 (2016)
Transforming growth factor-β (TGFβ) exerts key functions in fibrogenic cells, promoting fibrosis development in the liver and other organs. In contrast, the functions of TGFβ in liver epithelial cells are not well understood, despite their high level of responsiveness to TGFβ. We sought to deter...
Serum Amyloid A Induces Inflammation, Proliferation and Cell Death in Activated Hepatic Stellate Cells.
PLoS ONE 11(3):e0150893 (2016)
Serum amyloid A (SAA) is an evolutionary highly conserved acute phase protein that is predominantly secreted by hepatocytes. However, its role in liver injury and fibrogenesis has not been elucidated so far. In this study, we determined the effects of SAA on hepatic stellate cells (HSCs), the ma...
Contribution of Underlying Connective Tissue Cells to Taste Buds in Mouse Tongue and Soft Palate.
PLoS ONE 11(1):e0146475 (2016)
Taste buds, the sensory organs for taste, have been described as arising solely from the surrounding epithelium, which is in distinction from other sensory receptors that are known to originate from neural precursors, i.e., neural ectoderm that includes neural crest (NC). Our previous study sugg...
TLR4 Deficiency Protects against Hepatic Fibrosis and Diethylnitrosamine-Induced Pre-Carcinogenic Liver Injury in Fibrotic Liver.
PLoS ONE 11(7):e0158819 (2016)
The development of hepatocellular carcinoma (HCC) is a common consequence of advanced liver fibrosis but the interactions between fibrogenesis and carcinogenesis are still poorly understood. Recently it has been shown that HCC promotion depends on Toll-like receptor (TLR) 4. Pre-cancerogenous ev...
Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance.
Nature 527(7579):472 (2015)
The role of epithelial-to-mesenchymal transition (EMT) in metastasis is a longstanding source of debate, largely owing to an inability to monitor transient and reversible EMT phenotypes in vivo. Here we establish an EMT lineage-tracing system to monitor this process in mice, using a mesenchymal-...
Hepatocellular carcinoma originates from hepatocytes and not from the progenitor/biliary compartment.
Journal of Clinical Investigation 125(10):3891 (2015)
In many organs, including the intestine and skin, cancers originate from cells of the stem or progenitor compartment. Despite its nomenclature, the cellular origin of hepatocellular carcinoma (HCC) remains elusive. In contrast to most organs, the liver lacks a defined stem cell population for or...
HMGB1 and injury amplification.
Oncotarget 6(27):23048 (2015)
Origin and function of myofibroblasts in the liver.
Seminars in Liver Disease 35(2):e1 (2015)
Origin and function of myofibroblasts in the liver.
Seminars in Liver Disease 35(2):97 (2015)
Liver fibrosis contributes to many of the devastating complications of viral, toxic, fatty, and cholestatic liver disease. Understanding the cell populations that promote liver fibrosis and the molecular pathways through which they operate is essential for the development of antifibrotic therapi...
Hepatic inflammation and fibrosis: functional links and key pathways.
Hepatology 61(3):1066 (2015)
Inflammation is one of the most characteristic features of chronic liver disease of viral, alcoholic, fatty, and autoimmune origin. Inflammation is typically present in all disease stages and associated with the development of fibrosis, cirrhosis, and hepatocellular carcinoma. In the past decade...
High-yield and high-purity isolation of hepatic stellate cells from normal and fibrotic mouse livers.
Nature Protocols 10(2):305 (2015)
Hepatic stellate cells (HSCs) have been identified as the main fibrogenic cell type in the liver. Hence, efforts to understand hepatic fibrogenesis and to develop treatment strategies have focused on this cell type. HSC isolation, originally developed in rats, has subsequently been adapted to mi...
The HMGB1/RAGE axis triggers neutrophil-mediated injury amplification following necrosis.
Journal of Clinical Investigation 125(2):539 (2015)
In contrast to microbially triggered inflammation, mechanisms promoting sterile inflammation remain poorly understood. Damage-associated molecular patterns (DAMPs) are considered key inducers of sterile inflammation following cell death, but the relative contribution of specific DAMPs, including...
Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential.
Cell 160(1-2):269 (2015)
The stem cells that maintain and repair the postnatal skeleton remain undefined. One model suggests that perisinusoidal mesenchymal stem cells (MSCs) give rise to osteoblasts, chondrocytes, marrow stromal cells, and adipocytes, although the existence of these cells has not been proven through fa...
Mouse models of liver cancer.
Methods in Molecular Biology 1267:165 (2015)
Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide, and the third leading cause of cancer mortality. The great majority of patients are not eligible for curative therapies, and therapeutic approaches for advanced disease show only limited efficacy. Difficulties to treat HCC...
Comment on: HMGB1-dependent and -independent autophagy.
Autophagy 11(7):1187 (2015)
HMGB1 (high mobility group box 1), a ubiquitously expressed DNA-binding nucleoprotein, has not only been attributed with important functions in the regulation of gene expression but is thought to function as an important damage-associated molecular pattern in the extracellular space. Recently, c...
NAD(+) supplementation as a novel approach to cURIng HCC?
Cancer Cell 26(6):777 (2014)
In this issue of Cancer Cell, Tummala and colleagues demonstrate that unconventional prefoldin RPB5 interactor (URI) expression in hepatocytes leads to hepatocellular carcinoma (HCC) development by interacting with L-tryptophan/kynurenine/nicotinamide adenine dinucleotide (NAD(+)) metabolism. Th...
CCL20 mediates lipopolysaccharide induced liver injury and is a potential driver of inflammation and fibrosis in alcoholic hepatitis.
Gut 63(11):1782 (2014)
Chemokines are known to play an important role in the pathophysiology of alcoholic hepatitis (AH), a form of acute-on-chronic liver injury frequently mediated by gut derived lipopolysaccharide (LPS). In our study, we hypothesise that chemokine CCL20, one of the most upregulated chemokines in pat...
Cell death and cell death responses in liver disease: mechanisms and clinical relevance.
Gastroenterology 147(4):765 (2014)
Hepatocellular death is present in almost all types of human liver disease and is used as a sensitive parameter for the detection of acute and chronic liver disease of viral, toxic, metabolic, or autoimmune origin. Clinical data and animal models suggest that hepatocyte death is the key trigger ...