衰老肝细胞中基质金属蛋白酶的分泌受核因子-κB信号通路调控。
Senescent hepatocyte secretion of matrix metalloproteinases is regulated by nuclear factor-κB signaling.
作者信息
Zang Jinfeng, Sha Min, Zhang Chi, Ye Jun, Zhang Kezhi, Gao Junye
机构信息
Department of Hepatobiliary Surgery, Taizhou People's Hospital, The Fifth Affiliated Hospital of Medical School of Nantong University, China.
Central Laboratory, Taizhou People's Hospital, The Fifth Affiliated Hospital of Medical School of Nantong University, China.
出版信息
Life Sci. 2017 Dec 15;191:205-210. doi: 10.1016/j.lfs.2017.10.023. Epub 2017 Oct 17.
AIMS
Cellular senescence and matrix metalloproteinases (MMPs) play an important role in liver diseases. The source and regulating factors of MMPs in senescent hepatocytes are not known. We investigated whether senescent hepatocytes secreted MMPs and if this was regulated by nuclear factor (NF)-κB.
MATERIALS AND METHODS
The TGF-α transgenic mouse hepatocyte line AML12 was treated with HO to induce senescence. NF-κB signaling was examined by Western blotting and luciferase reporter assays. Quantitative reverse transcription polymerase chain reaction was used to evaluated expression of MMP-2, -9 and -13.
KEY FINDINGS
AML12 cells treated with HO showed the characteristic morphology of senescence. The activity of NF-κB and expression of MMP-2, -9 and -13 were increased in senescent AML12 cells. The NF-κB inhibitor BAY 11-7082 decreased the levels of MMPs.
SIGNIFICANCE
These results suggest that senescent hepatocytes are involved in the pathology of liver diseases through remodeling the extracellular matrix.
目的
细胞衰老和基质金属蛋白酶（MMPs）在肝脏疾病中起重要作用。衰老肝细胞中MMPs的来源和调节因子尚不清楚。我们研究了衰老肝细胞是否分泌MMPs以及这是否受核因子（NF）-κB调节。
材料与方法
用HO处理TGF-α转基因小鼠肝细胞系AML12以诱导衰老。通过蛋白质印迹法和荧光素酶报告基因测定法检测NF-κB信号传导。采用定量逆转录聚合酶链反应评估MMP-2、-9和-13的表达。
主要发现
用HO处理的AML12细胞呈现衰老的特征形态。衰老的AML12细胞中NF-κB活性以及MMP-2、-9和-13的表达增加。NF-κB抑制剂BAY 11-7082降低了MMPs的水平。
意义
这些结果表明衰老肝细胞通过重塑细胞外基质参与肝脏疾病的病理过程。
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