GPx7 ameliorates non-alcoholic steatohepatitis by regulating oxidative stress
GPx7 ameliorates non-alcoholic steatohepatitis by regulating oxidative stress
复制标题
DOI：
10.5483/bmbrep.2020.53.6.280
复制
发表时间：
2020-06-30
期刊：
影响因子：
3.8
通讯作者：
Kim, Jae-Woo
中科院分区：
文献类型：
--
作者：
Kim, Hyeon Ju;Lee, Yoseob;Kim, Jae-Woo
非酒精性脂肪性肝病（NAFLD）是最常见的肝病之一。NAFLD可进一步发展为不可逆的肝衰竭，如非酒精性脂肪性肝炎（NASH）纤维化和肝硬化。然而，NASH纤维化的特定调节剂尚未建立。在这里，我们发现谷胱甘肽过氧化物酶7（GPx 7）在NASH纤维化中显著表达。虽然GPx 7是一种保护其他器官的抗氧化酶，但GPx 7是否在NASH纤维化中发挥作用还有待研究。我们发现，在转化生长因子-β（TGF-β）和游离脂肪酸（FFA）处理的LX-2细胞中，GPx 7的敲低提高了促纤维化和促炎基因的表达以及胶原蛋白的合成。一致地，GPx 7在LX-2细胞中的过表达导致ROS产生的抑制，并减少促纤维化和促炎基因的表达。此外，通过敲低GPx 7显著加速由胆碱缺乏氨基酸限定的高脂肪饮食（CDAHFD）喂养诱导的NASH纤维化，如通过与CDAHFD对照小鼠相比上调的肝纤维化和炎症所证明的。总的来说，这些结果表明GPx 7可能是预防NAFLD进展和发展的新的治疗靶点。
Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. NAFLD can further progress to irreversible liver failure such as non-alcoholic steatohepatitis (NASH) fibrosis and cirrhosis. However, specific regulator of NASH-fibrosis has yet to be established. Here, we found that glutathione peroxidase 7 (GPx7) was markedly expressed in NASH fibrosis. Although GPx7 is an antioxidant enzyme protecting other organs, whether GPx7 plays a role in NASH fibrosis has yet to be studied. We found that knockdown of GPx7 in transforming growth factor-beta (TGF-beta) and free fatty acids (FFA)-treated LX-2 cells elevated the expression of pro-fibrotic and pro-inflammatory genes and collagen synthesis. Consistently, GPx7 overexpression in LX-2 cells led to the suppression of ROS production and reduced the expression of pro-fibrotic and pro-inflammatory genes. Further, NASH fibrosis induced by choline-deficient amino acid defined, high fat diet (CDAHFD) feeding was significantly accelerated by knockdown of GPx7, as evidenced by up-regulated liver fibrosis and inflammation compared with CDAHFD control mice. Collectively, these results suggest that GPx7 might be a novel therapeutic target to prevent the progression and development of NAFLD.