TY - JOUR
T1 - Transcriptional regulation of mouse mast cell protease-7 by TGF-β
AU - Funaba, Masayuki
AU - Ikeda, Teruo
AU - Murakami, Masaru
AU - Ogawa, Kenji
AU - Nishino, Yoshii
AU - Tsuchida, Kunihiro
AU - Sugino, Hiromu
AU - Abe, Matanobu
N1 - Funding Information:
We thank Drs. R. Derynck (Smad3 and Smad4 plasmids), M. Hibi (c- fos , c- jun and junB plasmids), Y. Kitamura (P7(-185)-luc and P7-mTRE-luc plasmids), E. Morii (P7(-185)-luc and P7-mTRE-luc plasmids), S. Nagata (TAM-67 plasmid), K. Shimozaki (TAM-67 plasmid), E.J. Stanbridge (SW480.7 cells) and X.-F. Wang (ALK5-TD plasmid) for providing plasmids and cell line. We also thank Drs. Takuya Murata, Akira Abe and Miki Hiraoka for critical reviewing of the manuscript. This work was supported by Grant-in-Aid for Scientific Research (13760214 and 15580268 to M.F. and 16580248 to T.I.) from Japan Society for the Promotion of Science and grants for Graduate Schools from The Foundation for Japanese Private School Promotion (to M.F., T.I. and M.M.).
PY - 2006/3
Y1 - 2006/3
N2 - Mouse mast cell protease-7 (mmcp-7) is a tryptase predominantly expressed in differentiated connective tissue-type mast cells. Previous study revealed that transforming growth factor-β (TGF-β) increases gene transcript of mmcp-7 in mast cells. The present study explored molecular mechanism of the up-regulation of mmcp-7 by TGF-β. Luciferase-based reporter assays using deletion and point mutations of mmcp-7 promoter showed a critical region spanning nt - 126 to - 122 relative to the transcriptional start site, a Smad-binding element, for transcriptional activation by the TGF-β pathway. In addition, a region from nt - 104 to - 98, a TPA-responsive element, was also necessary for the transactivation. Consistent with the current model for the TGF-β signaling, Smad4 was required for the transcription of mmcp-7 by Smad3, a signal mediator of TGF-β. Treatment with TGF-β in mast cells resulted in the differential gene induction of the AP-1 components, i.e., transient induction of c-fos but not of c-jun and junB. Expression of c-fos further enhanced Smad3 and Smad4-induced transcription of mmcp-7, whereas c-jun expression inhibited the transcription. Our results suggest that TGF-β stimulates mmcp-7 transcription through the Smad3-Smad4 pathway as well as c-fos induction, and that the AP-1 components distinctly related with the TGF-β pathway.
AB - Mouse mast cell protease-7 (mmcp-7) is a tryptase predominantly expressed in differentiated connective tissue-type mast cells. Previous study revealed that transforming growth factor-β (TGF-β) increases gene transcript of mmcp-7 in mast cells. The present study explored molecular mechanism of the up-regulation of mmcp-7 by TGF-β. Luciferase-based reporter assays using deletion and point mutations of mmcp-7 promoter showed a critical region spanning nt - 126 to - 122 relative to the transcriptional start site, a Smad-binding element, for transcriptional activation by the TGF-β pathway. In addition, a region from nt - 104 to - 98, a TPA-responsive element, was also necessary for the transactivation. Consistent with the current model for the TGF-β signaling, Smad4 was required for the transcription of mmcp-7 by Smad3, a signal mediator of TGF-β. Treatment with TGF-β in mast cells resulted in the differential gene induction of the AP-1 components, i.e., transient induction of c-fos but not of c-jun and junB. Expression of c-fos further enhanced Smad3 and Smad4-induced transcription of mmcp-7, whereas c-jun expression inhibited the transcription. Our results suggest that TGF-β stimulates mmcp-7 transcription through the Smad3-Smad4 pathway as well as c-fos induction, and that the AP-1 components distinctly related with the TGF-β pathway.
UR - https://www.scopus.com/pages/publications/33744533301
UR - https://www.scopus.com/pages/publications/33744533301#tab=citedBy
U2 - 10.1016/j.bbaexp.2006.04.003
DO - 10.1016/j.bbaexp.2006.04.003
M3 - Article
C2 - 16730810
AN - SCOPUS:33744533301
SN - 0167-4781
VL - 1759
SP - 166
EP - 170
JO - Biochimica et Biophysica Acta - Gene Structure and Expression
JF - Biochimica et Biophysica Acta - Gene Structure and Expression
IS - 3-4
ER -