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Sci Rep. 2016 May 5;6:24990. doi: 10.1038/srep24990.

Absence of cytoglobin promotes multiple organ abnormalities in aged mice.

Author information

1
Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
2
Department of Medical Nutrition, Graduate School of Human Life Science, Osaka City University, Osaka, Japan.
3
Department of Pathology, Takatsuki General Hospital, Takatsuki, Osaka, Japan.
4
PhoenixBio Co. Ltd., Hiroshima, Japan.

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 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.

PMID:
27146058
PMCID:
PMC4857093
DOI:
10.1038/srep24990
[Indexed for MEDLINE]
Free PMC Article

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