Absence of cytoglobin promotes multiple organ abnormalities in aged mice

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Abstract

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 NG-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.

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Thuy, L. T. T., Van Thuy, T. T., Matsumoto, Y., Hai, H., Ikura, Y., Yoshizato, K., & Kawada, N. (2016). Absence of cytoglobin promotes multiple organ abnormalities in aged mice. Scientific Reports, 6. https://doi.org/10.1038/srep24990

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