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Disruption of myofibroblastic Notch signaling attenuates liver fibrosis by modulating fibrosis progression and regression
by
Liu, Jingjing
, Ruan, Bai
, Duan, Juanli
, Song, Ping
, Han, Hua
, Wang, Lin
, Yue, Zhensheng
, Jiang, Zijian
in
Animals
/ Antibodies
/ Apoptosis
/ Bioinformatics
/ Carbon tetrachloride
/ Cell Proliferation - physiology
/ Cells, Cultured
/ Disruption
/ Fibrosis
/ Flox
/ Fluorides
/ Gene expression
/ Growth factors
/ Hepatic Stellate Cells - metabolism
/ Hepatic Stellate Cells - pathology
/ Hepatocytes
/ Laboratory animals
/ Liver
/ Liver - metabolism
/ Liver - pathology
/ Liver Cirrhosis - genetics
/ Liver Cirrhosis - metabolism
/ Liver Cirrhosis - pathology
/ Liver diseases
/ Male
/ Medical research
/ Mice
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Microscopy
/ Myofibroblasts - metabolism
/ Myofibroblasts - pathology
/ Proteins
/ Receptors, Notch - metabolism
/ Regression
/ Research Paper
/ Signal Transduction - physiology
/ Signaling
2021
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Disruption of myofibroblastic Notch signaling attenuates liver fibrosis by modulating fibrosis progression and regression
by
Liu, Jingjing
, Ruan, Bai
, Duan, Juanli
, Song, Ping
, Han, Hua
, Wang, Lin
, Yue, Zhensheng
, Jiang, Zijian
in
Animals
/ Antibodies
/ Apoptosis
/ Bioinformatics
/ Carbon tetrachloride
/ Cell Proliferation - physiology
/ Cells, Cultured
/ Disruption
/ Fibrosis
/ Flox
/ Fluorides
/ Gene expression
/ Growth factors
/ Hepatic Stellate Cells - metabolism
/ Hepatic Stellate Cells - pathology
/ Hepatocytes
/ Laboratory animals
/ Liver
/ Liver - metabolism
/ Liver - pathology
/ Liver Cirrhosis - genetics
/ Liver Cirrhosis - metabolism
/ Liver Cirrhosis - pathology
/ Liver diseases
/ Male
/ Medical research
/ Mice
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Microscopy
/ Myofibroblasts - metabolism
/ Myofibroblasts - pathology
/ Proteins
/ Receptors, Notch - metabolism
/ Regression
/ Research Paper
/ Signal Transduction - physiology
/ Signaling
2021
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Disruption of myofibroblastic Notch signaling attenuates liver fibrosis by modulating fibrosis progression and regression
by
Liu, Jingjing
, Ruan, Bai
, Duan, Juanli
, Song, Ping
, Han, Hua
, Wang, Lin
, Yue, Zhensheng
, Jiang, Zijian
in
Animals
/ Antibodies
/ Apoptosis
/ Bioinformatics
/ Carbon tetrachloride
/ Cell Proliferation - physiology
/ Cells, Cultured
/ Disruption
/ Fibrosis
/ Flox
/ Fluorides
/ Gene expression
/ Growth factors
/ Hepatic Stellate Cells - metabolism
/ Hepatic Stellate Cells - pathology
/ Hepatocytes
/ Laboratory animals
/ Liver
/ Liver - metabolism
/ Liver - pathology
/ Liver Cirrhosis - genetics
/ Liver Cirrhosis - metabolism
/ Liver Cirrhosis - pathology
/ Liver diseases
/ Male
/ Medical research
/ Mice
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Microscopy
/ Myofibroblasts - metabolism
/ Myofibroblasts - pathology
/ Proteins
/ Receptors, Notch - metabolism
/ Regression
/ Research Paper
/ Signal Transduction - physiology
/ Signaling
2021
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Disruption of myofibroblastic Notch signaling attenuates liver fibrosis by modulating fibrosis progression and regression
Journal Article
Disruption of myofibroblastic Notch signaling attenuates liver fibrosis by modulating fibrosis progression and regression
2021
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Overview
The phenotypic transformation of hepatic myofibroblasts (MFs) is involved in the whole process of the progression and regression of liver fibrosis. Notch signaling has been demonstrated to modulate the fibrosis. In this study, we found that Notch signaling in MFs was overactivated and suppressed with the progression and regression of hepatic fibrosis respectively, by detecting Notch signaling readouts in MFs. Moreover, we inactivated Notch signaling specifically in MFs with Sm22α
-RBPj
mice (RBPj
), and identified that MFs-specific down-regulation of Notch signaling significantly alleviated CCl
-induced liver fibrosis during the progression and regression. During the progression of liver fibrosis, MFs-specific blockade of Notch signaling inhibited the activation of HSCs to MFs and increases the expression of MMPs to reduce the deposition of ECM. During the regression of fibrosis, blocking Notch signaling in MFs increased the expression of HGF to promote proliferation in hepatocytes and up-regulated the expression of pro-apoptotic factors, Ngfr and Septin4, to induce apoptosis of MFs, thereby accelerating the reversal of fibrosis. Collectively, the MFs-specific disruption of Notch signaling attenuates liver fibrosis by modulating fibrosis progression and regression, which suggests a promising therapeutic strategy for liver fibrosis.
Publisher
Ivyspring International Publisher Pty Ltd,Ivyspring International Publisher
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