Wu Chi, Song Xiaozhen, Zhang Miaoxin, Yang Longjun, Lu Panpan, Ding Qiang, Liu Mei
Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
J Cell Mol Med. 2024 Dec;28(23):e70267. doi: 10.1111/jcmm.70267.
There are three homologous proteins (α, β and γ) in the growth arrest and DNA damage 45 (Gadd45) family. These proteins act as cellular responders to physiological and environmental stimuli. Gadd45β plays a significant role in the pathogenesis of liver diseases. Liver injury and growth stimulation increase expression of Gadd45β, which promotes cell survival, growth and proliferation in normal liver cells. By contrast, Gadd45β plays a role in promoting apoptosis and inhibiting tumour function in hepatocellular carcinoma (HCC). Currently, it is believed that Gadd45β benefits the liver through two different pathways: binding to MAPK kinase 6 (MKK6) to increase PCD induced by p38 (inhibiting tumours) or binding to constitutive androstane receptor (CAR) to jointly activate transcription of liver synthesis metabolism (promoting liver regeneration). This article aims to systematically review the role of Gadd45β in liver diseases, including its regulatory mechanism on expression and involvement in liver cell damage, inflammation, fibrosis and HCC. In conclusion, we explore the potential of targeting Gadd45β as a therapeutic strategy for liver diseases.
生长停滞与DNA损伤诱导蛋白45（Gadd45）家族中有三种同源蛋白（α、β和γ）。这些蛋白作为细胞对生理和环境刺激的应答分子。Gadd45β在肝脏疾病的发病机制中起重要作用。肝损伤和生长刺激会增加Gadd45β的表达，这在正常肝细胞中可促进细胞存活、生长和增殖。相比之下，Gadd45β在肝细胞癌（HCC）中发挥促进细胞凋亡和抑制肿瘤功能的作用。目前认为，Gadd45β通过两种不同途径对肝脏产生有益作用：与丝裂原活化蛋白激酶激酶6（MKK6）结合以增加由p38诱导的程序性细胞死亡（抑制肿瘤），或与组成型雄烷受体（CAR）结合以共同激活肝脏合成代谢的转录（促进肝再生）。本文旨在系统综述Gadd45β在肝脏疾病中的作用，包括其对表达的调控机制以及在肝细胞损伤、炎症、纤维化和HCC中的参与情况。总之，我们探讨了将Gadd45β作为肝脏疾病治疗策略靶点的潜力。
