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1,25‐Dihydroxyvitamin D 3 induction of the tissue‐type plasminogen activator gene is mediated through its multihormone‐responsive enhancer
Author(s) -
Merchiers Pascal,
Bulens Frank,
Stockmans Ingrid,
De Vriese Astrid,
Convents Renilde,
Bouillon Roger,
Collen Désiré,
Belayew Alexandra,
Carmeliet Geert
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01337-x
Subject(s) - enhancer , microbiology and biotechnology , retinoic acid , plasminogen activator , chemistry , transgene , activator (genetics) , gene , biology , gene expression , biochemistry , endocrinology
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 D 3 [1,25(OH) 2 D 3 ] 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) 2 D 3 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.