Translational augmentation of pro‐matrix metalloproteinase 3 (prostromelysin 1) and tissue inhibitor of metalloproteinases (TIMP)‐1 mRNAs induced by epidermal growth factor in human uterine cervical fibroblasts

FEBS Letters

Mori, Yo¹  Hosono, Tetsuji¹  Sato, Takashi¹  Nagase, Hideaki²  Ito, Akira¹ 

[1] Department of Biochemistry, Tokyo College of Pharmacy, 1432 Horinouchi, Hachioji, Tokyo 192-03, Japan;Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160-7421, USA

关键词: Matrix metalloproteinase 3;    Prostromelysin 1;    Tissue inhibitor of metalloproteinases-1;    Epidermal growth factor;    Human uterine cervical fibroblast;    EGF;    epidermal growth factor;    hEGF;    21-leu recombinant human-like EGF;    IL-1;    interleukin 1;    TNFα;    tumor necrosis factor α;    MMP;    matrix metalloproteinase;    TIMP-1;    tissue inhibitor of metalloproteinases-1;    TPA;    12-o-tetradecanoyl-phorbol-13-acetate;    TRE;    TPA-responsive element;    AP-1;    activator protein-1;    FBS;    fetal bovine serum;    MEM;    Eagle's minimum essential medium;    PBS;    phosphate buffer saline;    LAH;    lactalbumin hydrolysate;    GAPDH;    glyceraldehyde-3-phosphate dehydrogenase;    SDS-PAGE;    sodium dodecyl sulfate-polyacrylamide gel electrophoresis;   

DOI  :  10.1016/0014-5793(96)00081-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The mechanisms by which epidermal growth factor (EGF) enhances the production of pro-matrix metalloproteinase 3 (proMMP-3/prostromelysin 1) and tissue inhibitor of metalloproteinases (TIMP)-1 were investigated using human uterine cervical fibroblasts. The treatment of the cells with EGF for 24 h resulted in about 5–6-fold increase in the production of proMMP-3 and TIMP-1 compared with the untreated control cells. This increase was accompanied by an increase of proMMP-3 and TIMP-1 mRNAs. However, an about 3- and 2-fold increase in the production of proMMP-3 and TIMP-1, respectively, was observed as early as 1 h after the treatment of the cells with EGF, and it was not accompanied by any apparent increase in proMMP-3 and TIMP-1 mRNAs. This early effect of EGF on the enhanced production of proMMP-3 and TIMP-1 was not inhibited by actinomycin D, even though actinomycin D inhibited the synthesis of the total RNA in both the EGF-treated and untreated cells. These results indicate that EGF enhances the apparent production of proMMP-3 and TIMP-1 by two mechanisms: one by the accelerated translation of their mRNAs; and the other by the enhanced transcription of their genes. The former event takes place much earlier than the latter.

【 授权许可】

Unknown