Rdh13 deficiency weakens carbon tetrachloride-induced liver injury by regulating Spotl4 and Cyp2e1 expression levels  

作　　者：Xiaofang Cui Benting Ma Yan Wang Yan Chen Chunling Shen Ying Kuang Jian Fei Lungen Lu Zhugang Wang 

机构地区：[1]State Key Laboratory of Medical Genomics,Research Center for Experimental Medicine,Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [2]Shanghai Research Center for Model Organisms,Shanghai 201203,China [3]Department of Gastroenterology,Shanghai First People s Hospital,Shanghai Jiao Tong University,Shanghai 200080,China

出　　处：《Frontiers of Medicine》2019年第1期104-111,共8页医学前沿（英文版）

基　　金：grants from the National Natural Science Foundation of China (No.81430028);the Ministry of Science and Technology of China (No.2011BAI15B02);the grants from the Science and Technology Commission of Shanghai Municipality (Nos.13DZ2280600 and 15DZ2290800);the grant from Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University (No.81300776).

摘　　要：Mitochondrion-localized retinol dehydrogenase 13 (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 injury induced by carbon tetrachloride (CC14). 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 Rdhl3 1 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 WT after CC14 exposure. The ablation of Rdhl3 gene decreased the expression levels of thyroid hormone-inducible nuclear protein 14 (Spot14) and cytochrome P450 (Cyp2el) in the liver, especially after CC14 treatment for 48 h. These data suggested that the alleviated liver damage induced by CC14 in Rdh13^-/- mice was caused by Cyp2el enzymes, which promoted reductive CC14 metabolism by altering the status of thyroxine metabolism. This result further implicated Rdhl3 as a potential drug target in preventing chemically induced liver injury.

关 键 词：RETINOL DEHYDROGENASE 13 carbon TETRACHLORIDE acute liver injury Cyp2el Spot14 

分 类 号：R[医药卫生]