MMP-9调控EGFR信号通路对肝再生的作用研究
发布时间：2019-05-29 06:33
【摘要】：众多人体器官中,唯独肝脏具有强大的修复与再生功能,深入阐明这种再生功能的机制有利于治疗各种肝脏疾病。目前研究认为肝再生(Liver regeneration)是一个非常复杂但受精确调控的过程,并把涉及其中的机制与因子主要分为三类：细胞因子信号通路、生长因子信号通路和代谢网络信号通路。已有研究报道基质金属蛋白酶-9(matrix metalloproteinase-9, MMP-9)在肝再生中扮演极其重要的积极角色,但是其中相关机制尚未完全明了。本次研究利用MMP-9敲除鼠,通过建立百分之七十肝切除模型来探讨MMP-9调控表皮生长因子受体(epidermal growth factor receptor, EFGR)信号通路在肝再生中的作用及其具体机制。方法：肝切除模型分为以下三组：1.1假手术组(施行开关腹手术)；1.2对照组(野生型小鼠建立肝切除模型)；1.3敲除组(MMP-9敲除鼠建立肝切除模型)。术后在相应时间点采血取肝,检测肝再生情况、EGFR配体、EGFR信号通路下游蛋白表达水平等。结果：MMP-9敲除小鼠较野生型小鼠在肝切除术后：肝再生延迟,早期EGFR配体双调蛋白(Amphiregulin, AR)和肝素结合型表皮生长因子(heparin-binding epidermal growth factors, HB-EGF)表达下调,EGFR激活延迟。同时EGFR下游信号转导与转录激活因子-3(Signal transducer and activator of transcription-3, STAT3),核因子κB (NF-κB),细胞周期蛋D1(cyclinD1)表达与EGFR一致下调。结论：MMP-9在肝再生中的重要作用是通过调控EGFR配体来影响EGFR信号通路的激活,从而进一步影响细胞增生信号。
[Abstract]:Among many human organs, only the liver has strong repair and regeneration function, which is beneficial to the treatment of various liver diseases. At present, it is considered that liver regeneration (Liver regeneration) is a very complex but accurately regulated process, and the mechanisms and factors involved in it are mainly divided into three categories: cytokine signal pathway, growth factor signal pathway and metabolic network signal pathway. It has been reported that matrix metalloprotease-9 (matrix metalloproteinase-9, MMP-9) plays an important and active role in liver regeneration, but the related mechanisms are not yet fully understood. In this study, MMP-9 knockout mice were used to establish a 70% hepatectomy model to investigate the role of MMP-9 in regulating (epidermal growth factor receptor, EFGR) signaling pathway of epidermis growth factor receptor in liver regeneration and its specific mechanism. Methods: the hepatectomy model was divided into the following three groups: 1.1. false operation group (open abdominal operation), 1.2control group (wild type mice established hepatectomy model), 1.3knockout group (MMP-9 knockout mice established hepatectomy model). The liver was collected at the corresponding time point after operation to detect liver regeneration, EGFR ligands and the expression of downstream proteins in EGFR signaling pathway. Results: compared with wild type mice, MMP-9 knockout mice delayed liver regeneration and down-regulated the expression of EGFR ligand biregulatory protein (Amphiregulin, AR) and heparin binding epidermis growth factor (heparin-binding epidermal growth factors, HB-EGF) in early stage. EGFR activation delay. At the same time, the expression of signal transduction and transcription activating factor-3 (Signal transducer and activator of transcription-3, STAT3, nuclear factor kappa B (NF- kappa B) and cell cycle egg D1 (cyclinD1) downstream of EGFR were down-regulated with EGFR. Conclusion: the important role of MMP-9 in liver regeneration is to regulate EGFR ligands to affect the activation of EGFR signaling pathway, thus further affecting cell proliferation signal.
【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R657.3
[Abstract]:Among many human organs, only the liver has strong repair and regeneration function, which is beneficial to the treatment of various liver diseases. At present, it is considered that liver regeneration (Liver regeneration) is a very complex but accurately regulated process, and the mechanisms and factors involved in it are mainly divided into three categories: cytokine signal pathway, growth factor signal pathway and metabolic network signal pathway. It has been reported that matrix metalloprotease-9 (matrix metalloproteinase-9, MMP-9) plays an important and active role in liver regeneration, but the related mechanisms are not yet fully understood. In this study, MMP-9 knockout mice were used to establish a 70% hepatectomy model to investigate the role of MMP-9 in regulating (epidermal growth factor receptor, EFGR) signaling pathway of epidermis growth factor receptor in liver regeneration and its specific mechanism. Methods: the hepatectomy model was divided into the following three groups: 1.1. false operation group (open abdominal operation), 1.2control group (wild type mice established hepatectomy model), 1.3knockout group (MMP-9 knockout mice established hepatectomy model). The liver was collected at the corresponding time point after operation to detect liver regeneration, EGFR ligands and the expression of downstream proteins in EGFR signaling pathway. Results: compared with wild type mice, MMP-9 knockout mice delayed liver regeneration and down-regulated the expression of EGFR ligand biregulatory protein (Amphiregulin, AR) and heparin binding epidermis growth factor (heparin-binding epidermal growth factors, HB-EGF) in early stage. EGFR activation delay. At the same time, the expression of signal transduction and transcription activating factor-3 (Signal transducer and activator of transcription-3, STAT3, nuclear factor kappa B (NF- kappa B) and cell cycle egg D1 (cyclinD1) downstream of EGFR were down-regulated with EGFR. Conclusion: the important role of MMP-9 in liver regeneration is to regulate EGFR ligands to affect the activation of EGFR signaling pathway, thus further affecting cell proliferation signal.
【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R657.3
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