TWEAK通过NF-κB途径促进大鼠成纤维细胞表达基质金属蛋白酶9  

Tumor necrosis factor-like weak inducer of apoptosis promotes expression of matrix metalloproteinase 9 in rat cardiac fibroblasts via the nuclear factor-κB pathway

作　　者：王德金[1] 任满意[2] 陈慧娜[1] 王旭平[3] 隋树建[1] 

机构地区：[1]山东大学第二医院心内科,济南250033 [2]山东省胸科医院心内科,济南250013 [3]山东大学齐鲁医院心内科,教育部和卫生部心血管重构与功能研究重点实验室,济南250012

出　　处：《山东大学学报（医学版）》2011年第11期13-17,共5页Journal of Shandong University:Health Sciences

基　　金：山东省自然科学基金资助项目(Y2007C073);山东省科技攻关计划(2007GG10002014)

摘　　要：目的研究肿瘤坏死因子样凋亡微弱诱导剂(TWEAK)影响大鼠心肌成纤维细胞(CFs)增殖和胶原合成的作用机制。方法采用胰酶消化法培养新生Wistar大鼠CFs,加入重组人TWEAK(rhTWEAK)和NF-κB抑制剂PDTC干预,qRT-PCR检测核转录因子NF-κB和金属蛋白酶9(MMP9)mRNA,Western blot检测NF-κB和MMP9蛋白表达,四甲基偶氮唑蓝(MTT)法测定细胞增殖。结果 rhTWEAK作用后NF-κB和MMP9 mRNA表达上调,同时蛋白表达明显增加,PDTC可抑制MMP9蛋白表达和细胞增殖。结论 TWEAK可通过NF-κB途径促进大鼠心肌成纤维细胞表达MMP9。Objective To investigate the mechanism and effects of tumor necrosis factor-like weak inducer of apoptosis（TWEAK） on the proliferation and collagen synthesis in cultured rat cardiac fibroblasts（CFs）.Methods Cultured CFs from neonatal Wistar rats were isolated by trypsinization and treated with recombinant human TWEAK（rhTWEAK） and PDTC（NF-κB specific inhibitor）.mRNA and protein expressions of NF-κB and MMP9 were detected by qRT-PCR and Western blot,respectively.CFs proliferation was examined by MTT.Results rhTWEAK significantly elevated mRNA and protein expressions of NF-κB and MMP9.PDTC could inhibit MMP9 protein expression and CFs proliferation induced by NF-κB′s activation.Conclusion TWEAK can promote expressions of matrix metalloproteinase 9 in rat cardiac fibroblasts via the NF-κB pathway.

关 键 词：肿瘤坏死因子样凋亡微弱诱导剂 心肌成纤维细胞 NF-ΚB 基质金属蛋白酶9 心肌纤维化 

分 类 号：R542.2[医药卫生—心血管疾病]