Expression profiles uncover the relationship between erythropoietin and cell proliferation in rat hepatocytes after a partial hepatectomy

Cellular & Molecular Biology Letters

Yajuan Yang²  Yongkang Chen³  Tingting He²  Yun Zhou²  Yunqing Liu²  Jihong Zhang²  Cunshuan Xu¹ 

[1] College of Life Science, Henan Normal University, Xinxiang, P.R. China$$Key Laboratory for Cell Differentiation Regulation, Xinxiang, P.R. China$$;College of Life Science, Henan Normal University, Xinxiang, P.R. China$$;College of Life Science and Technology, Jinan University, Guangzhou, P.R. China$$

关键词: Rat liver regeneration;    Erythropoietin;    Rat Genome 230 2.0 Microarray;    Gene expression profiles;    Gene synergetic effect;   

DOI  :  10.2478/s11658-014-0198-0

学科分类：分子生物学，细胞生物学和基因

来源: Uniwersytet Wroclawski * Wydzial Biotechnologii / University of Wroclaw, Faculty of Biotechnology

【 摘 要 】

Erythropoietin (EPO) has a beneficial effect on hepatic cell proliferation during liver regeneration. However, the underlying mechanism has not yet been elucidated. To uncover the proliferation response of EPO in rat liver regeneration after partial hepatectomy (PH) at the cellular level, hepatocytes (HCs) were isolated using Percoll density gradient centrifugation. The genes of the EPO-mediated signaling pathway and the target genes of the transcription factor (TF) in the pathway were identified in a pathway and TF database search. Their expression profiles were then detected using Rat Genome 230 2.0 Microarray. The results indicated that the EPO-mediated signaling pathway is involved in 19 paths and that 124 genes participate, of which 32 showed significant changes and could be identified as liver regeneration-related genes. In addition, 443 targets regulated by the TFs of the pathway and 60 genes associated with cell proliferation were contained in the array. Subsequently, the synergetic effect of these genes in liver regeneration was analyzed using the E(t) mathematical model based on their expression profiles. The results demonstrated that the E(t) values of paths 3, 8, 12 and 14–17 were significantly strengthened in the progressing phase of liver regeneration through the RAS/MEK/ERK or PI3K/AκT pathways. The synergetic effect of the target genes, in parallel with target-related cell proliferation, was also enhanced 12–72 h after PH, suggesting a potential positive effect of EPO on HC proliferation during rat liver regeneration. These data imply that the EPO receptor may allow EPO to promote HC proliferation through paths 3, 8, 12 and 14–17, mediating the RAS/MEK/ERK and PI3K/AκT pathways in rat liver regeneration after PH.

【 授权许可】

Unknown