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Hepatocyte mitochondria-derived danger signals directly activate hepatic stellate cells and drive progression of liver fibrosis
by
Kuramitsu, Kaori
, An, Ping
, Zhao, Shuangshuang
, Lai, Michelle
, Miyamoto, Makoto
, Sverdlov, Deanna Y.
, Popov, Yury V.
, Wei, Lin-Lin
, Vaid, Kahini A.
in
13/1
/ 13/106
/ 13/51
/ 38
/ 38/39
/ 631/80/304
/ 64
/ 64/60
/ 692/308/1426
/ 692/699/1503/1607
/ 692/699/1503/1607/1605
/ 692/699/1503/1607/2751
/ 82/51
/ 82/80
/ 96
/ Adult
/ Aged
/ Aged, 80 and over
/ Alarmins - immunology
/ Alarmins - metabolism
/ Animals
/ Apoptosis - immunology
/ Bile
/ Cell activation
/ Damage patterns
/ Diagnostic systems
/ Disease Models, Animal
/ Disease Progression
/ Female
/ Fibrosis
/ Hepatic Stellate Cells - immunology
/ Hepatocytes
/ Hepatocytes - cytology
/ Hepatocytes - immunology
/ Hepatocytes - metabolism
/ Humanities and Social Sciences
/ Humans
/ Inflammation
/ Inflammatory response
/ Injuries
/ Liver
/ Liver - cytology
/ Liver - drug effects
/ Liver - immunology
/ Liver - pathology
/ Liver Cirrhosis - chemically induced
/ Liver Cirrhosis - immunology
/ Liver Cirrhosis - pathology
/ Liver diseases
/ Macrophages
/ Macrophages - immunology
/ Male
/ Mice
/ Middle Aged
/ Mitochondria
/ Mitochondria - metabolism
/ Mitochondrial DNA
/ Morbidity
/ multidisciplinary
/ Myeloid cells
/ Non-alcoholic Fatty Liver Disease - immunology
/ Non-alcoholic Fatty Liver Disease - pathology
/ Phagocytes
/ Phagocytosis - immunology
/ Scars
/ Science
/ Science (multidisciplinary)
/ Stellate cells
/ Thioacetamide - toxicity
/ Young Adult
2020
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Hepatocyte mitochondria-derived danger signals directly activate hepatic stellate cells and drive progression of liver fibrosis
by
Kuramitsu, Kaori
, An, Ping
, Zhao, Shuangshuang
, Lai, Michelle
, Miyamoto, Makoto
, Sverdlov, Deanna Y.
, Popov, Yury V.
, Wei, Lin-Lin
, Vaid, Kahini A.
in
13/1
/ 13/106
/ 13/51
/ 38
/ 38/39
/ 631/80/304
/ 64
/ 64/60
/ 692/308/1426
/ 692/699/1503/1607
/ 692/699/1503/1607/1605
/ 692/699/1503/1607/2751
/ 82/51
/ 82/80
/ 96
/ Adult
/ Aged
/ Aged, 80 and over
/ Alarmins - immunology
/ Alarmins - metabolism
/ Animals
/ Apoptosis - immunology
/ Bile
/ Cell activation
/ Damage patterns
/ Diagnostic systems
/ Disease Models, Animal
/ Disease Progression
/ Female
/ Fibrosis
/ Hepatic Stellate Cells - immunology
/ Hepatocytes
/ Hepatocytes - cytology
/ Hepatocytes - immunology
/ Hepatocytes - metabolism
/ Humanities and Social Sciences
/ Humans
/ Inflammation
/ Inflammatory response
/ Injuries
/ Liver
/ Liver - cytology
/ Liver - drug effects
/ Liver - immunology
/ Liver - pathology
/ Liver Cirrhosis - chemically induced
/ Liver Cirrhosis - immunology
/ Liver Cirrhosis - pathology
/ Liver diseases
/ Macrophages
/ Macrophages - immunology
/ Male
/ Mice
/ Middle Aged
/ Mitochondria
/ Mitochondria - metabolism
/ Mitochondrial DNA
/ Morbidity
/ multidisciplinary
/ Myeloid cells
/ Non-alcoholic Fatty Liver Disease - immunology
/ Non-alcoholic Fatty Liver Disease - pathology
/ Phagocytes
/ Phagocytosis - immunology
/ Scars
/ Science
/ Science (multidisciplinary)
/ Stellate cells
/ Thioacetamide - toxicity
/ Young Adult
2020
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Hepatocyte mitochondria-derived danger signals directly activate hepatic stellate cells and drive progression of liver fibrosis
by
Kuramitsu, Kaori
, An, Ping
, Zhao, Shuangshuang
, Lai, Michelle
, Miyamoto, Makoto
, Sverdlov, Deanna Y.
, Popov, Yury V.
, Wei, Lin-Lin
, Vaid, Kahini A.
in
13/1
/ 13/106
/ 13/51
/ 38
/ 38/39
/ 631/80/304
/ 64
/ 64/60
/ 692/308/1426
/ 692/699/1503/1607
/ 692/699/1503/1607/1605
/ 692/699/1503/1607/2751
/ 82/51
/ 82/80
/ 96
/ Adult
/ Aged
/ Aged, 80 and over
/ Alarmins - immunology
/ Alarmins - metabolism
/ Animals
/ Apoptosis - immunology
/ Bile
/ Cell activation
/ Damage patterns
/ Diagnostic systems
/ Disease Models, Animal
/ Disease Progression
/ Female
/ Fibrosis
/ Hepatic Stellate Cells - immunology
/ Hepatocytes
/ Hepatocytes - cytology
/ Hepatocytes - immunology
/ Hepatocytes - metabolism
/ Humanities and Social Sciences
/ Humans
/ Inflammation
/ Inflammatory response
/ Injuries
/ Liver
/ Liver - cytology
/ Liver - drug effects
/ Liver - immunology
/ Liver - pathology
/ Liver Cirrhosis - chemically induced
/ Liver Cirrhosis - immunology
/ Liver Cirrhosis - pathology
/ Liver diseases
/ Macrophages
/ Macrophages - immunology
/ Male
/ Mice
/ Middle Aged
/ Mitochondria
/ Mitochondria - metabolism
/ Mitochondrial DNA
/ Morbidity
/ multidisciplinary
/ Myeloid cells
/ Non-alcoholic Fatty Liver Disease - immunology
/ Non-alcoholic Fatty Liver Disease - pathology
/ Phagocytes
/ Phagocytosis - immunology
/ Scars
/ Science
/ Science (multidisciplinary)
/ Stellate cells
/ Thioacetamide - toxicity
/ Young Adult
2020
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Hepatocyte mitochondria-derived danger signals directly activate hepatic stellate cells and drive progression of liver fibrosis
Journal Article
Hepatocyte mitochondria-derived danger signals directly activate hepatic stellate cells and drive progression of liver fibrosis
2020
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Overview
Due to their bacterial ancestry, many components of mitochondria share structural similarities with bacteria. Release of molecular danger signals from injured cell mitochondria (mitochondria-derived damage-associated molecular patterns, mito-DAMPs) triggers a potent inflammatory response, but their role in fibrosis is unknown. Using liver fibrosis resistant/susceptible mouse strain system, we demonstrate that mito-DAMPs released from injured hepatocyte mitochondria (with mtDNA as major active component) directly activate hepatic stellate cells, the fibrogenic cell in the liver, and drive liver scarring. The release of mito-DAMPs is controlled by efferocytosis of dying hepatocytes by phagocytic resident liver macrophages and infiltrating Gr-1(+) myeloid cells. Circulating mito-DAMPs are markedly increased in human patients with non-alcoholic steatohepatitis (NASH) and significant liver fibrosis. Our study identifies specific pathway driving liver fibrosis, with important diagnostic and therapeutic implications. Targeting mito-DAMP release from hepatocytes and/or modulating the phagocytic function of macrophages represents a promising antifibrotic strategy.
Progressive fibrosis is a driver of morbidity and mortality in many chronic liver diseases, but the underlying mechanisms are incompletely understood. Here, the authors show that mitochondria-derived damage-associated molecular patterns are released from injured hepatocytes and can trigger fibrogenic activation of hepatic stellate cells.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/106
/ 13/51
/ 38
/ 38/39
/ 64
/ 64/60
/ 82/51
/ 82/80
/ 96
/ Adult
/ Aged
/ Animals
/ Bile
/ Female
/ Fibrosis
/ Hepatic Stellate Cells - immunology
/ Humanities and Social Sciences
/ Humans
/ Injuries
/ Liver
/ Liver Cirrhosis - chemically induced
/ Liver Cirrhosis - immunology
/ Male
/ Mice
/ Non-alcoholic Fatty Liver Disease - immunology
/ Non-alcoholic Fatty Liver Disease - pathology
/ Scars
/ Science
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