模型化研究Nogo-B促进STAT3磷酸化与肝细胞增殖和再生

Model Study on Nogo-B promoting STAT3 Phosphorylation and Hepatocyte Proliferation and Regeneration

基于Hill动力学与Michaelis-Menten方程建立理论模型,研究肝细胞中内质网定位的蛋白Nogo-B表达促进信号传导与转录激活因子STAT3磷酸化及肝细胞增殖与肝再生,理论模型考虑Nogo-B-IL-6/STAT3通路.研究表明,肝细胞中的IL-6与sIL6R结合生成复合物IS,IS促进Gp130和JAK2诱导信号通路;随着JAK2浓度的上升,JAK2与Nogo-B引起STAT3的磷酸化,产生大量P-STAT3,随着P-STAT3浓度的上升,引起STAT3二聚即产生PP-STAT3;随后转移到细胞核,激活基因转录,激活了Nogo-B-IL-6/STAT3通路,进而促进肝细胞增殖和肝再生.理论结果符合实验结果,揭示了Nogo-B在肝细胞增殖和肝再生中的作用,并为设计肝损伤后的康复,以及肝再生提供理论依据.

Based on hill dynamics and Michaelis Menten equation,a theoretical model was established to study the expression of protein Nogo-B localized in endoplasmic reticulum in hepatocytes,promote the phosphorylation of signal transducer and activator of transcription(STAT3),hepatocyte proliferation and liver regeneration.The theoretical model considered Nogo-B-interleukin 6(IL-6)-STAT3 pathway,Studies have shown that IL-6 in hepatocytes binds to soluble IL-6 receptor(sIL6R)to form complex is,which promotes the induction of signal pathway by soluble glycoprotein 130(Gp130)and Janus kinase 2 gene(JAK2).With the increase of JAK2 concentration,JAK2 and Nogo-B cause the phosphorylation of STAT3 and produce a large amount of P-STAT3(phosphorylated signal translator and activator of transcription 3).With the increase of P-STAT3 concentration,it causes the dimerization of STAT3,PP-STAT3(phosphorylated signal translator and activator of transcription 3),which is then transferred to the nucleus,activate gene transcription,activate Nogo-B-IL-6-STAT3 pathway,and then promote hepatocyte proliferation and liver regeneration.The theoretical results are consistent with the experimental results,reveal and determine the role of Nogo-B in hepatocyte proliferation and liver regeneration,and provide a theoretical basis for the design of rehabilitation and liver regeneration after liver injury.