Rdh13 deficiency weakens carbon tetrachloride-induced liver injury by regulating Spot14 and Cyp2e1 expression levels
2019
Mitochondrion-localized
retinol dehydrogenase13 (Rdh13) is a
short-chain dehydrogenase/reductase involved in vitamin A metabolism in both humans and mice. We previously generated Rdh13 knockout mice and showed that Rdh13 deficiency causes severe acute retinal light damage. In this study, considering that Rdh13 is highly expressed in mouse liver, we further evaluated the potential effect of Rdh13 on
liver injuryinduced by carbon tetrachloride (
CCl4). Although Rdh13 deficiency showed no significant effect on liver histology and physiological functions under regular culture, the Rdh13–/– mice displayed an attenuated response to
CCl4-induced
liver injury. Their livers also exhibited less histological changes and contained lower levels of liver-related metabolism enzymes compared with the livers of wild-type (WT) mice. Furthermore, the Rdh13–/– mice had Rdh13 deficiency and thus their liver cells were protected from apoptosis, and the quantity of their proliferative cells became lower than that in WTafter
CCl4exposure. The ablation of Rdh13 gene decreased the expression levels of thyroid hormone-inducible nuclear protein 14 (Spot14) and cytochrome P450 (
Cyp2e1) in the liver, especially after
CCl4treatment for 48 h. These data suggested that the alleviated liver damage induced by
CCl4in Rdh13–/– mice was caused by
Cyp2e1enzymes, which promoted reductive
CCl4metabolism by altering the status of thyroxine metabolism. This result further implicated Rdh13 as a potential drug target in preventing chemically induced
liver injury.
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