Selective overexpression of cytoglobin in stellate cells attenuates thioacetamide-induced liver fibrosis in mice View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Nguyen Thi Thanh Hai, Le Thi Thanh Thuy, Akira Shiota, Chiho Kadono, Atsuko Daikoku, Dinh Viet Hoang, Ninh Quoc Dat, Misako Sato-Matsubara, Katsutoshi Yoshizato, Norifumi Kawada

ABSTRACT

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 (HSCCygb-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. HSCsCygb-TG were resistant to H2O2-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. More... »

PAGES

17860

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-36215-4

DOI

http://dx.doi.org/10.1038/s41598-018-36215-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1110510371

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30552362


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