Yang Xianguang, Chen Xuelin, Xia Cong, Li Shuaihong, Zhu Lin, Xu Cunshuan
College of Life Science, Henan Normal University, Xinxiang, Henan Province, China.
State Key Laboratory Cultivation Base for Cell Differentiation Regulation and Henan Bioengineering Key Laboratory, Henan Normal University, Xinxiang, Henan Province, China.
Histol Histopathol. 2020 Sep;35(9):949-960. doi: 10.14670/HH-18-218. Epub 2020 Apr 16.
Gadd45α (growth arrest and DNA damage inducible alpha) is a member of a group of genes whose transcript levels are increased following stressful conditions that lead to growth arrest and treatment with agents that lead to DNA damage. Gadd45α is upregulated in liver cirrhosis (LC), hepatic cancer (HC), acute liver failure (AHF) and non-alcoholic fatty liver disease(NAFLD). Here, we investigated the essential differences in the Gadd45α signaling pathway in these diseases at the transcriptional level. The results showed that 44, 46, 71 and 27 genes significant changes in these diseases, and the H-cluster showed that the expression of the Gadd45α signaling-related genes was significantly different in the four liver diseases. DAVID functional analysis showed that the Gadd45α signaling pathway-related genes were mainly involved in cell adhesion and migration, cell proliferation, apoptosis, stress and inflammatory responses, etc. Ingenuity pathway analysis (IPA) software was used to predict the functions of the Gadd45α signaling-related genes, and the results indicated that there were significant changes in cell differentiation, DNA damage repair, autophagy, apoptosis and necrosis. Gadd45α signaling pathway is involved in four kinds of liver disease and regulates a variety of activities via P38 MAPK, NF-κB, mTOR/STAT3, P21, PCNA, PI3K/Akt and other signaling pathways. Modulation of Gadd45α may be exploited to prevent the progression of liver disease, and to identify specific treatments for different stages of liver disease. In summary, the Gadd45α signaling pathway is involved in four kinds of liver disease and regulates a variety of physiological activities through various signaling pathways.
生长停滞和DNA损伤诱导蛋白α（Gadd45α）是一组基因的成员，其转录水平在导致生长停滞的应激条件下以及用导致DNA损伤的试剂处理后会升高。Gadd45α在肝硬化（LC）、肝癌（HC）、急性肝衰竭（AHF）和非酒精性脂肪性肝病（NAFLD）中上调。在此，我们在转录水平上研究了这些疾病中Gadd45α信号通路的本质差异。结果显示，在这些疾病中有44、46、71和27个基因发生了显著变化，并且H聚类表明Gadd45α信号相关基因的表达在四种肝病中存在显著差异。DAVID功能分析表明，Gadd45α信号通路相关基因主要参与细胞黏附与迁移、细胞增殖、凋亡、应激和炎症反应等。使用Ingenuity通路分析（IPA）软件预测Gadd45α信号相关基因的功能，结果表明在细胞分化、DNA损伤修复、自噬、凋亡和坏死方面存在显著变化。Gadd45α信号通路参与四种肝病，并通过P38丝裂原活化蛋白激酶（MAPK）、核因子κB（NF-κB）、哺乳动物雷帕霉素靶蛋白/信号转导子和转录激活子3（mTOR/STAT3）、P21、增殖细胞核抗原（PCNA）、磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/Akt）等信号通路调节多种活动。对Gadd45α的调节可能有助于预防肝病进展，并为肝病不同阶段确定特异性治疗方法。总之，Gadd45α信号通路参与四种肝病，并通过各种信号通路调节多种生理活动。
