Cytokines and signaling pathways regulating matrix metalloproteinase-9 (MMP-9) expression in corneal epithelial cells.
Cytokines and signaling pathways regulating matrix metalloproteinase-9 (MMP-9) expression in corneal epithelial cells.
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细胞因子和信号通路调节角膜上皮细胞中基质金属蛋白酶 9 (MMP-9) 的表达。
DOI：
10.1002/jcp.21869
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发表时间：
2009-11
影响因子：
5.6
通讯作者：
Fini, M. Elizabeth
中科院分区：
文献类型：
--
作者：
Gordon, Gabriel M.;Ledee, Dolena R.;Feuer, William J.;Fini, M. Elizabeth
基质金属蛋白酶-9（MMP-9）是众所周知的许多细胞过程（包括伤口愈合）的调节剂和效应剂。在角膜中，过多或过少的MMP-9都可能对整体伤口修复有害。我们研究了分泌因子以及细胞内信号传导途径和介导这种调节的启动子序列。原代培养的兔角膜上皮细胞用各种细胞因子单独或以不同组合处理，并通过凝胶酶谱法评估MMP-9诱导。使用药理学抑制剂来确定由所测试的细胞因子诱导的细胞内信号传导途径，并且创建缺失启动子构建体来确定参与细胞因子调节的MMP-9启动子的区域，从而评估结合MMP-9启动子的确切转录因子。我们发现，两个细胞因子家族，TGF-β和IL-1，以同种型非特异性方式叠加作用，诱导MMP-9在这种细胞类型中。我们的数据表明，TGF-β介导的MMP-9诱导可能受到NF-κ B、Smad 3和JNK通路的调节，而IL-1β介导的诱导可能受到NF-κ B和p38通路的调节。抑制p38、NF-kB或JNK通路可显著降低但不消除基础MMP-9水平。ERK通路的抑制对MMP-9介导的表达没有影响，无论是在处理的还是未处理的共转染细胞中。
Matrix metalloproteinase-9 (MMP-9) is a well known regulator and effecter of many cellular processes including wound healing. In the cornea, either too much or too little MMP-9 can be detrimental to overall wound repair. We investigated the secreted factors as well as the intracellular signaling pathways and the promoter sequences that mediate this regulation. Primary culture rabbit corneal epithelial cells were treated with various cytokines alone or in different combinations and MMP-9 induction was assessed by gel zymography. Pharmacological inhibitors were used to determine the intracellular signaling pathways induced by the cytokines tested and deletion promoter constructs were created to determine the regions of the MMP-9 promoter involved in the cytokine regulation, thereby assessing the exact transcription factors binding the MMP-9 promoter. We found that two cytokine families, TGF-β and IL-1, act additively in an isoform non-specific manner to induce MMP-9 in this cell type. Our data suggest TGF-β mediated MMP-9 induction may be regulated by the NF-kB, Smad3, and JNK pathways, whereas the IL-1β mediated induction may be regulated by the NF-kB and p38 pathways. Inhibition of the p38, NF-kB, or JNK pathways significantly reduced, but did not abrogate, basal MMP-9 levels. Inhibition of the ERK pathway did not have an effect on MMP-9 mediated expression in either the treated or untreated co-transfected cells.
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影响因子：
4.8
作者：
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通讯作者：
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