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Selective overexpression of cytoglobin in stellate cells attenuates thioacetamide-induced liver fibrosis in mice
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Selective overexpression of cytoglobin in stellate cells attenuates thioacetamide-induced liver fibrosis in mice
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Selective overexpression of cytoglobin in stellate cells attenuates thioacetamide-induced liver fibrosis in mice
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Journal Article
Selective overexpression of cytoglobin in stellate cells attenuates thioacetamide-induced liver fibrosis in mice
2018
Overview
Cytoglobin (CYGB), discovered in hepatic stellate cells (HSCs), is known to possess a radical scavenger function, but its pathophysiological roles remain unclear. Here, for the first time, we generated a new transgenic (TG) mouse line in which both Cygb and mCherry reporter gene expression were under the control of the native
Cygb
gene promoter. We demonstrated that the expression of Cygb-mCherry was related to endogenous
Cygb
in adult tissues by tracing mCherry fluorescence together with DNA, mRNA, and protein analyses. Administration of a single dose (50 mg/kg) of thioacetamide (TAA) in Cygb-TG mice resulted in lower levels of alanine transaminase and oxidative stress than those in WT mice. After 10 weeks of TAA administration, Cygb-TG livers exhibited reduced neutrophil accumulation, cytokine expression and fibrosis but high levels of quiescent HSCs. Primary HSCs isolated from Cygb-TG mice (HSC
Cygb-TG
) exhibited significantly decreased mRNA levels of α-smooth muscle actin (αSMA), collagen 1α1, and transforming growth factor β-3 after 4 days in culture relative to WT cells. HSCs
Cygb-TG
were resistant to H
2
O
2
-induced αSMA expression. Thus, cell-specific overexpression of Cygb attenuates HSC activation and protects mice against TAA-induced liver fibrosis presumably by maintaining HSC quiescence. Cygb is a potential new target for antifibrotic approaches.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
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/ Actin
/ Alanine
/ Animals
/ Collagen
/ DNA
/ Fibrosis
/ Hepatic Stellate Cells - enzymology
/ Hepatic Stellate Cells - metabolism
/ Humanities and Social Sciences
/ Liver Cirrhosis - chemically induced
/ Liver Cirrhosis - prevention & control
/ Luminescent Proteins - biosynthesis
/ Luminescent Proteins - genetics
/ Mice
/ Science
