| First Author | Thi Thanh Hai N | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 17860 |
| PubMed ID | 30552362 | Mgi Jnum | J:268728 |
| Mgi Id | MGI:6271863 | Doi | 10.1038/s41598-018-36215-4 |
| Citation | Thi Thanh Hai N, et al. (2018) Selective overexpression of cytoglobin in stellate cells attenuates thioacetamide-induced liver fibrosis in mice. Sci Rep 8(1):17860 |
| abstractText | 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 alpha-smooth muscle actin (alphaSMA), collagen 1alpha1, and transforming growth factor beta-3 after 4 days in culture relative to WT cells. HSCs(Cygb-TG) were resistant to H2O2-induced alphaSMA 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. |
