Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 166-170 |
| Number of pages | 5 |
| Journal | Biochimica et Biophysica Acta - Gene Structure and Expression |
| Volume | 1759 |
| Issue number | 3-4 |
| DOIs | |
| Publication status | Published - 01-03-2006 |
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All Science Journal Classification (ASJC) codes
- Structural Biology
- Biophysics
- Biochemistry
- Genetics
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Transcriptional regulation of mouse mast cell protease-7 by TGF-β. / Funaba, Masayuki; Ikeda, Teruo; Murakami, Masaru; Ogawa, Kenji; Nishino, Yoshii; Tsuchida, Kunihiro; Sugino, Hiromu; Abe, Matanobu.
In: Biochimica et Biophysica Acta - Gene Structure and Expression, Vol. 1759, No. 3-4, 01.03.2006, p. 166-170.Research output: Contribution to journal › Article
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
PY - 2006/3/1
Y1 - 2006/3/1
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.
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U2 - 10.1016/j.bbaexp.2006.04.003
DO - 10.1016/j.bbaexp.2006.04.003
M3 - Article
C2 - 16730810
AN - SCOPUS:33744533301
VL - 1759
SP - 166
EP - 170
JO - Biochimica et Biophysica Acta - Gene Structure and Expression
JF - Biochimica et Biophysica Acta - Gene Structure and Expression
SN - 0167-4781
IS - 3-4
ER -