1,25‐Dihydroxyvitamin D3 induction of the tissue‐type plasminogen activator gene is mediated through its multihormone‐responsive enhancer

FEBS Letters

Bouillon, Roger¹  Carmeliet, Geert¹  De Vriese, Astrid²  Merchiers, Pascal²  Convents, Renilde¹  Bulens, Frank²  Stockmans, Ingrid¹  Belayew, Alexandra²  Collen, Désiré² 

[1] Laboratory for Experimental Medicine and Endocrinology, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium;Center for Molecular and Vascular Biology, University of Leuven, Campus Gasthuisberg, O and N, Herestraat 49, B-3000 Leuven, Belgium

关键词: 1;    25-Dihydroxy vitamin D3;    Tissue-type plasminogen activator;    Enhancer;    Vitamin D-responsive element;    Probability model;    1;    25(OH)2D3;    1;    25-dihydroxyvitamin D3;    CAT;    chloramphenicol acetyltransferase;    DRn;    direct repeat separated by n nucleotides;    EMSA;    electrophoretic mobility shift assay;    IPn;    inverted palindrome separated by n nucleotides;    NF-I;    nuclear factor-I;    oc;    osteocalcin;    Paln;    palindromic element separated by n nucleotides;    RA;    retinoic acid;    RAR;    RA receptor;    RARE;    RA-responsive element;    RXR;    retinoid X receptor;    TK;    thymidine kinase;    t-PA;    tissue-type plasminogen activator;    VDR;    vitamin D receptor;    VDRE;    vitamin D-responsive element;   

DOI  :  10.1016/S0014-5793(99)01337-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Tissue-type plasminogen activator (t-PA) is a positive modulator of the plasminogen-plasmin system, which is involved in bone remodeling. In the present study, 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] was found to stimulate t-PA gene expression in ROS17/2.8 osteosarcoma cells. Transient transfection analysis and in vitro DNA binding studies identified two vitamin D-responsive elements (VDRE) in the human t-PA enhancer. The first VDRE (bp −7175 to −7146) comprised an inverted palindrome separated by 9 bp (IP9) overlapping a palindrome separated by 3 bp. The second VDRE (bp −7315 to −7302) is an IP2 element overlapping the previously identified retinoic acid-responsive element. 1,25(OH)₂D₃ treatment of primary osteoblasts derived from t-PAlacZ transgenic mice containing 9 kb of 5′ sequence of the human t-PA gene increased the number of lacZ-positive cells, fitting with the probability model of enhancer function.

【 授权许可】

Unknown