Kitamura M, Maruyama N, Mitarai T, Nagasawa R, Yokoo T, Sakai O
Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Biochem Biophys Res Commun. 1994 Sep 15;203(2):1333-8. doi: 10.1006/bbrc.1994.2328.
The aim of this study is to examine the transcriptional regulation of matrix metalloproteinase transin in glomerular mesangial cells responding to inflammatory cytokines and heparin. Northern blot analysis revealed that IL-1 beta preferentially induced transin mRNA. The stimulatory effect was not specific to transin, and upregulation of procollagen alpha 1(IV), laminin B2 and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNAs was also observed. After IL-1 stimulation, expression of the transin transcript increased progressively for up to 48 hours, differing from the limited induction of procollagen alpha 1(IV) or TIMP-1. When mesangial cells were stimulated by IL-1 beta in the presence of heparin, transin expression was markedly suppressed in a dose-dependent manner. The inhibitory effect of heparin was specific to transin, and induction of procollagen alpha 1(IV), laminin B2 or TIMP-1 by IL-1 beta was not affected. These findings revealed the selective counter regulation by IL-1 beta and heparin of the transin expression in mesangial cells.
本研究的目的是检测肾小球系膜细胞中基质金属蛋白酶（transin）在对炎性细胞因子和肝素反应时的转录调控。Northern印迹分析显示，白细胞介素-1β（IL-1β）优先诱导transin mRNA表达。这种刺激作用并非transin所特有，同时还观察到Ⅳ型前胶原α1、层粘连蛋白B2和金属蛋白酶组织抑制剂-1（TIMP-1）mRNA的上调。IL-1刺激后，transin转录本的表达持续增加长达48小时，这与Ⅳ型前胶原α1或TIMP-1的有限诱导不同。当系膜细胞在肝素存在的情况下受到IL-1β刺激时，transin表达以剂量依赖的方式显著受到抑制。肝素的抑制作用对transin具有特异性，IL-1β对Ⅳ型前胶原α1、层粘连蛋白B2或TIMP-1的诱导不受影响。这些发现揭示了IL-1β和肝素对系膜细胞中transin表达的选择性反向调节。
