Tenascin-C upregulation by transforming growth factor-β in human dermal broblasts involves Smad3, Sp1, and Ets1

被引：105

作者：

Jinnin, M

Ihn, H

Asano, Y

Yamane, K

Trojanowska, M

Tamaki, K

机构：

[1] Univ Tokyo, Fac Med, Dept Dermatol, Bunkyo Ku, Tokyo 1138655, Japan

[2] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA

来源：

ONCOGENE | 2004年 / 23卷 / 09期

关键词：

CREB-binding protein; P300; extracellular matrix;

D O I：

10.1038/sj.onc.1207064

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In cultured human dermal fibroblasts, transforming growth factor ( TGF)-beta induced the mRNA expression of tenascin-C (TN-C). The molecular mechanism(s) underlying this process is not presently understood. In this study, we performed serial 50 deletion and a transient transfection analysis to de. ne a region in the TN-C promoter mediating the inducible responsiveness to TGF-beta. This region contains an atypical nucleotide recognition element for the Smad family of transcriptional regulators. A DNA affinity precipitation assay revealed that Smad2/ Smad3 bound to this site in a transient and specific manner. Overexpression of Smad3 or Smad4 activated the TN-C promoter activity and superinduced the TN-C promoter activity stimulated by TGF-beta. Moreover, simultaneous cotransfection of Smad3 and Smad4 activated the TN-C promoter activity in a synergistic manner. Mutation of the Smad-binding sites, the Ets-binding sites, or Sp1/3-binding sites in the TN-C promoter abrogated the TGF-beta/Smad-inducible promoter activity. Immunoprecipitation analysis revealed that Smad3, Sp1, and Ets1 form a transcriptionally active complex. Furthermore, the interaction between Smads and CBP/p300 in TGF-beta signaling was confirmed. These findings demonstrate the existence of a novel, functional binding element in the proximal region of the TN-C promoter mediating responsiveness to TGF-beta involving Smad3/4, Sp1, Ets1, and CBP/p300.

引用

页码：1656 / 1667

页数：12

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