TY - JOUR
T1 - Identification of tocopherol-associated protein as an activin/TGF-β-inducible gene in mast cells
AU - Funaba, Masayuki
AU - Murakami, Masaru
AU - Ikeda, Teruo
AU - Ogawa, Kenji
AU - Tsuchida, Kunihiro
AU - Sugino, Hiromu
N1 - Funding Information:
We thank Dr. A.F. Parlow for providing recombinant human activin A and the National Hormone and Pituitary Program at the NIDDK. We thank Drs. Xianxin Hua, Naohiro Inohara, Yukihiko Kitamura, Takeyoshi Koseki, Harvey F. Lodish, Eiichi Morii, Xiao-Fan Wang, Malcolm Whitman for providing plasmids. We also thank Drs. Takuya Murata and Tetsuya Mizutani for critical reviewing of the manuscript. This work was supported by Grant-in-Aid for Scientific Research (15580268 to M.F., 17580262 to M.M. 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., M.M. and T.I.).
PY - 2006/8
Y1 - 2006/8
N2 - Previous studies have demonstrated that treatment with activin A and TGF-β1, members of the TGF-β family, stimulated maturation of mouse bone marrow-derived cultured mast cells (BMMC), which was characterized by morphology and gene expression of mouse mast cell proteases (mmcps). In order to gain a better understanding of activin A- and TGF-β1-induced maturation in mast cells, we investigated the genes that were up-regulated in response to treatment with these two members of the TGF-β family. The cDNA microarray analyses indicated that in BMMC, five genes were induced by treatment with 4 nM activin A for 2 h. Tocopherol-associated protein (Tap) was one of the induced genes, and the Tap induction in response to activin A treatment was confirmed by real-time RT-PCR analyses. Treatment with TGF-β1 at 200 pM but not BMP-2 at 4 nM also increased Tap gene transcript in BMMC. Activin A-induced Tap expression was detected in BMMC but not in RAW264 macrophage-like cells, B16 melanoma cells or P19 embryonic carcinoma cells. Treatment with > 1 μM SB431542, an inhibitor of activin and TGF-β type I receptors ALK4/5, reduced responsiveness of Tap expression to TGF-β1, whereas < 0.5 μM SB431542 effectively reduced TGF-β1-induced expression of mmcp-1 and mmcp-7. These results suggest that inhibitory effects of SB431542 are different between TGF-β-induced genes. Reporter assays indicated that Tap expression enhances transcription mediated by the activin/TGF-β pathway. Thus, the present results suggest that Tap induction in response to activin/TGF-β occurs predominantly in mast cells and serves as a positive regulator in activin/TGF-β signaling.
AB - Previous studies have demonstrated that treatment with activin A and TGF-β1, members of the TGF-β family, stimulated maturation of mouse bone marrow-derived cultured mast cells (BMMC), which was characterized by morphology and gene expression of mouse mast cell proteases (mmcps). In order to gain a better understanding of activin A- and TGF-β1-induced maturation in mast cells, we investigated the genes that were up-regulated in response to treatment with these two members of the TGF-β family. The cDNA microarray analyses indicated that in BMMC, five genes were induced by treatment with 4 nM activin A for 2 h. Tocopherol-associated protein (Tap) was one of the induced genes, and the Tap induction in response to activin A treatment was confirmed by real-time RT-PCR analyses. Treatment with TGF-β1 at 200 pM but not BMP-2 at 4 nM also increased Tap gene transcript in BMMC. Activin A-induced Tap expression was detected in BMMC but not in RAW264 macrophage-like cells, B16 melanoma cells or P19 embryonic carcinoma cells. Treatment with > 1 μM SB431542, an inhibitor of activin and TGF-β type I receptors ALK4/5, reduced responsiveness of Tap expression to TGF-β1, whereas < 0.5 μM SB431542 effectively reduced TGF-β1-induced expression of mmcp-1 and mmcp-7. These results suggest that inhibitory effects of SB431542 are different between TGF-β-induced genes. Reporter assays indicated that Tap expression enhances transcription mediated by the activin/TGF-β pathway. Thus, the present results suggest that Tap induction in response to activin/TGF-β occurs predominantly in mast cells and serves as a positive regulator in activin/TGF-β signaling.
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U2 - 10.1016/j.bbamcr.2006.06.002
DO - 10.1016/j.bbamcr.2006.06.002
M3 - Article
C2 - 16872693
AN - SCOPUS:33747082659
SN - 0167-4889
VL - 1763
SP - 900
EP - 906
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
IS - 8
ER -