Expression of Cellular Prion Protein in Activated Hepatic Stellate Cells

Ikeda, Kazuo; Kawada, Norifumi; Wang, Yan Qing; Kadoya, Hirokazu; Nakatani, Kazuki; Sato, Makoto; Kaneda, Kenji

doi:10.1016/s0002-9440(10)65683-0

Cited by 35 publications

(32 citation statements)

References 27 publications

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“…Confusion has increased in the past decade because a neural crest origin has also been suggested based on stellate cells' expression of several neural crest markers, including glial fibrillary acidic protein (GFAP), nestin, neurotrophins and their receptors, N-CAM, synaptophysin, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), Rho-N, N-cadherin (192), as well as cellular prion protein (249). However, fate mapping studies of neural crest-derived cells in developing mouse liver have recently failed to localize to hepatic stellate cells during late gestation (94,193), undermining the possibility of a neural origin.…”

Section: A Embryologic Origin(s)mentioning

confidence: 99%

Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

Friedman

2008

Physiological Reviews

2,388

2,549

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The hepatic stellate cell has surprised and engaged physiologists, pathologists, and hepatologists for over 130 years, yet clear evidence of its role in hepatic injury and fibrosis only emerged following the refinement of methods for its isolation and characterization. The paradigm in liver injury of activation of quiescent vitamin A-rich stellate cells into proliferative, contractile, and fibrogenic myofibroblasts has launched an era of astonishing progress in understanding the mechanistic basis of hepatic fibrosis progression and regression. But this simple paradigm has now yielded to a remarkably broad appreciation of the cell's functions not only in liver injury, but also in hepatic development, regeneration, xenobiotic responses, intermediary metabolism, and immunoregulation. Among the most exciting prospects is that stellate cells are essential for hepatic progenitor cell amplification and differentiation. Equally intriguing is the remarkable plasticity of stellate cells, not only in their variable intermediate filament phenotype, but also in their functions. Stellate cells can be viewed as the nexus in a complex sinusoidal milieu that requires tightly regulated autocrine and paracrine cross-talk, rapid responses to evolving extracellular matrix content, and exquisite responsiveness to the metabolic needs imposed by liver growth and repair. Moreover, roles vital to systemic homeostasis include their storage and mobilization of retinoids, their emerging capacity for antigen presentation and induction of tolerance, as well as their emerging relationship to bone marrow-derived cells. As interest in this cell type intensifies, more surprises and mysteries are sure to unfold that will ultimately benefit our understanding of liver physiology and the diagnosis and treatment of liver disease.

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Section: A Embryologic Origin(s)mentioning

confidence: 99%

Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

Friedman

2008

Physiological Reviews

2,388

2,549

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“…Molecular approaches to explore stellate cell gene regulation during early activation have identified differentially up-regulated genes (13)(14)(15). An advantage to the stellate cell system in these studies has been the opportunity to analyze "in vivo" gene expression in freshly purified, homogenous cell isolates.…”

Section: Initiation: Paracrine Stimulation and Transcriptional Eventsmentioning

confidence: 99%

Molecular Regulation of Hepatic Fibrosis, an Integrated Cellular Response to Tissue Injury

Friedman

2000

Journal of Biological Chemistry

1,950

1,681

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“…Immunohistochemistry for anti-BMP-7 was performed according to the method previously described. 23 The sections were blocked against endogenous peroxidase using 3% H 2 O 2 . The sections were treated first with a 1:1000-diluted goat polyclonal anti-BMP-7 (Sigma) and then with horseradish peroxidaseconjugated anti-immunoglobulins.…”

Section: Analyses Of Hepatic Fibrosis and Immunohistochemistrymentioning

confidence: 99%

Adenovirus-mediated expression of BMP-7 suppresses the development of liver fibrosis in rats

Kinoshita

Iimuro

Otogawa

et al. 2007

Gut

141

110

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Background: Liver cirrhosis, which is caused by the accumulation of extracellular matrix materials, is a serious clinical problem that can progress to hepatic failure. Transforming growth factor-b (TGFb) plays a pivotal role in extracellular matrix production, but bone morphogenetic protein (BMP)-7, a member of the TGFb superfamily, can antagonise the fibrogenic activity of TGFb. Aim: In this study, we examined whether adenovirus-mediated overexpression of BMP-7 (Ad-BMP-7) antagonised the effect of TGFb in vitro and in vivo. Methods and results: In primary cultured rat stellate cells and the LX-2 human stellate cell line, induction of BMP-7 by Ad-BMP-7 infection decreased the expression of collagen 1A2 mRNA and smooth muscle a-actin in the presence or absence of TGFb, via Smad 1/5/8 phosphorylation. BMP-7 triggered the mRNA expression of inhibitors of differentiation 2 (Id2) in LX-2. Although endogenous expression of BMP-7 was hardly detectable, Smad1 and Id2 overexpression increased BMP-7 expression in LX-2. A liver fibrosis model was induced by the repetitive intraperitoneal injection of thioacetamide (200 mg/kg body weight) twice per week for up to 7 weeks. In rats administered Ad-BMP-7 via the tail vein, hydroxyproline content and the areas stained by Sirius red dye in the liver were significantly reduced compared to controls. Ad-Id2 also reduced fibrosis.Conclusion: These data demonstrate that BMP-7, Smad 1/5/8 and Ids interact to antagonise hepatic fibrogenesis.

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Expression of Cellular Prion Protein in Activated Hepatic Stellate Cells

Cited by 35 publications

References 27 publications

Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

Molecular Regulation of Hepatic Fibrosis, an Integrated Cellular Response to Tissue Injury

Adenovirus-mediated expression of BMP-7 suppresses the development of liver fibrosis in rats

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