| First Author | Thuy le TT | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 24990 | PubMed ID | 27146058 |
| Mgi Jnum | J:269209 | Mgi Id | MGI:6216359 |
| Doi | 10.1038/srep24990 | Citation | Thuy le TT, et al. (2016) Absence of cytoglobin promotes multiple organ abnormalities in aged mice. Sci Rep 6:24990 |
| abstractText | Cytoglobin (Cygb) was identified in hepatic stellate cells (HSCs) and pericytes of all organs; however, the effects of Cygb on cellular functions remain unclear. Here, we report spontaneous and age-dependent malformations in multiple organs of Cygb(-/-) mice. Twenty-six percent of young Cygb(-/-) mice (<1 year old) showed heart hypertrophy, cystic disease in the kidney or ovary, loss of balance, liver fibrosis and lymphoma. Furthermore, 71.3% (82/115) of aged Cygb(-/-) mice (1-2 years old) exhibited abnormalities, such as heart hypertrophy and cancer development in multiple organs; by contrast, 5.8% (4/68) of aged wild-type (WT) mice had abnormalities (p < 0.0001). Interestingly, serum and urine analysis demonstrated that the concentration of nitric oxide metabolites increased significantly in Cygb(-/-) mice, resulting in an imbalance in the oxidative stress and antioxidant defence system that was reversed by N(G)-monomethyl-L-arginine treatment. A senescent phenotype and evidence of DNA damage were found in primary HSCs and the liver of aged Cygb(-/-) mice. Moreover, compared with HSC(+/+), HSC(-/-) showed high expression of Il-6 and chemokine mRNA when cocultured with mouse Hepa 1-6 cells. Thus, the absence of Cygb in pericytes provokes organ abnormalities, possibly via derangement of the nitric oxide and antioxidant defence system and through accelerated cellular senescence. |
