Eight paths of ERK1/2 signalling pathway regulating hepatocyte proliferation in rat liver regeneration

Journal of genetics

G. P. Wang¹  C. S. Xu1 2¹  C. F. Chang¹  J. Y. Fan²  J. W. Li¹ 

[1] College of Life Sciences, Henan Normal University, Xinxiang 453007, Henan Province, People’s Republic of China$$;Key Laboratory for Cell Differentiation Regulation, Xinxiang 453007, Henan Province, People’s Republic of China$$

关键词: liver regeneration;    hepatocytes;    ERK1/2 signalling pathway;    proliferation;    Rat Genome 230 2.0 Array;    gene expression profile.;   

DOI  :  

学科分类：生物科学（综合）

来源: Indian Academy of Sciences

【 摘 要 】

Although it is known that hormones, growth factors and integrin promote hepatocyte proliferation in liver regeneration (LR) through ERK1/2 signalling pathway, reports about regulating processes of its intracellular paths in hepatocytes of LR are limited. This study aims at exploring which paths of ERK1/2 signalling pathway participate in the regulation of rat LR, especially in hepatocyte proliferation, and how they do so. In all, 14 paths and 165 genes are known to be involved in ERK1/2 signalling pathway. Of them, 161 genes are included in Rat Genome 230 2.0 Array. This array was used to detect expression changes of genes related to ERK1/2 signalling pathway in isolated hepatocytes of rat LR, showing that 60 genes were related to hepatocytes of LR. In addition, bioinformatics and systems biology methods were used to analyse the roles of 14 above paths in regenerating hepatocytes. We found that three paths, RTK → SHC → GRB2/SOS → RAS → RAF, Integrin 𝛽 → FAK → RAC → PAK → RAF and G 𝛽 𝛾 → PI3K 𝛽 𝛾 → RAC → PAK → RAF, promoted the G1 phase progression of hepatocytes by activating ERK1/2. A further four paths, Gq → PLC 𝛽 → PKC → SRC/PYK2 → GRB2/SOS → RAS → RAF, RTK → PLC 𝛾 → PKC → SRC/PYK2 → GRB2/SOS → RAS → RAF, Integrin 𝛽 → FAK/SRC → GRB2/SOS → RAS → RAF and Integrin 𝛽→ FAK → RAC → PAK → RAF, advanced the cell progression of S phase and G2/M checkpoint by activating ERK1/2, and so did PP1/2 → Mek1/2 by decreasing the negative influence on ERK1/2. At the late phase of LR, G𝛼s → AC → EPAC → Rap1 → Raf blocked hepatocyte proliferation by decreasing the activity of ERK1/2 and so did PP1/2 → Mek1/2. In summary, 60 genes and 8 paths of ERK1/2 signalling pathway regulated hepatocyte proliferation in rat LR.

【 授权许可】

Unknown