Wang Gaiping, Cheng Liya, Chen Meng, Zhao Congcong, Gao Mingxin, Huang Tiantian, Chu Peipei, Xu Cunshuan
College of Life Science, Henan Normal University, Xinxiang, 453007, Henan, China.
State Key Laboratory Cultivation Base for Cell Differentiation Regulation, Henan Normal University, Xinxiang, Henan, China.
Biochem Genet. 2019 Jun;57(3):382-402. doi: 10.1007/s10528-018-9900-7. Epub 2019 Jan 1.
Regenerating islet-derived protein (Reg) could participate in the occurrence of diabetes mellitus, inflammation, tumors, and other diseased or damaged tissues. However, the correlation of Reg with acute hepatic failure (AHF) and hepatocellular carcinoma (HCC) is poorly defined. To reveal the expression profiles of Reg family and their possible regulatory roles in AHF and HCC, rat models of HCC and AHF were separately established, and Rat Genome 230 2.0 was used to detect expression profiles of Reg-mediated signaling pathways-associated genes from liver tissues in AHF and HCC. The results showed that a total of 79 genes were significantly changed. Among these genes, 67 genes were the AHF-specific genes, 45 genes were the HCC-specific genes, and 33 genes were the common genes. Then, K-means clustering classified these genes into 4 clusters based on the gene expression similarity, and DAVID analysis showed that the above altered genes were mainly associated with stress response, inflammatory response, and cell cycle regulation. Thereafter, IPA software was used to analyze potential effects of these genes, and the predicted results suggested that the Reg-mediated JAK/STAT, NF-κB, MAPK (ERK1/2, P38 and JNK), PLC, and PI3K/AKT signaling pathways may account for the activated inflammation and cell proliferation, and the attenuated apoptosis and cell death during the occurrence of AHF and HCC.
再生胰岛衍生蛋白(Reg)可参与糖尿病、炎症、肿瘤及其他患病或受损组织的发生过程。然而,Reg与急性肝衰竭(AHF)和肝细胞癌(HCC)之间的相关性尚不明确。为揭示Reg家族的表达谱及其在AHF和HCC中可能的调控作用,分别建立了HCC和AHF大鼠模型,并使用大鼠基因组230 2.0检测AHF和HCC肝组织中Reg介导的信号通路相关基因的表达谱。结果显示,共有79个基因发生显著变化。其中,67个基因为AHF特异性基因,45个基因为HCC特异性基因,33个基因为共同基因。然后,K均值聚类根据基因表达相似性将这些基因分为4个簇,DAVID分析表明上述改变的基因主要与应激反应、炎症反应和细胞周期调控相关。此后,使用IPA软件分析这些基因的潜在作用,预测结果表明Reg介导的JAK/STAT、NF-κB、MAPK(ERK1/2、P38和JNK)、PLC和PI3K/AKT信号通路可能是AHF和HCC发生过程中炎症激活、细胞增殖以及凋亡和细胞死亡减弱的原因。