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Molecular and Cellular Biology, January 2009, p. 425-434, Vol. 29, No. 2
0270-7306/09/$08.00+0     doi:10.1128/MCB.01278-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Transcription Factor Fli1 Regulates Collagen Fibrillogenesis in Mouse Skin

Yoshihide Asano,^1, Margaret Markiewicz,^1, Masahide Kubo,^1, Gabor Szalai,² Dennis K. Watson,² and Maria Trojanowska^1*

Division of Rheumatology and Immunology,¹ Department of Pathology and Laboratory Medicine and Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina 29425²

Received 12 August 2008/ Returned for modification 14 September 2008/ Accepted 26 October 2008

Biosynthesis of fibrillar collagen in the skin is precisely regulated to maintain proper tissue homeostasis; however, the molecular mechanisms involved in this process remain largely unknown. Transcription factor Fli1 has been shown to repress collagen synthesis in cultured dermal fibroblasts. This study investigated the role of Fli1 in regulation of collagen biosynthesis in mice skin in vivo using mice with the homozygous deletion of the C-terminal transcriptional activation (CTA) domain of the Fli1 gene (Fli1^CTA/CTA). Skin analyses of the Fli1 mutant mice revealed a significant upregulation of fibrillar collagen genes at mRNA level, as well as increased collagen content as measured by acetic acid extraction and hydroxyproline assays. In addition, collagen fibrils contained ultrastructural abnormalities including immature thin fibrils and very thick irregularly shaped fibrils, which correlated with the reduced levels of decorin, fibromodulin, and lumican. Fibroblasts cultured from the skin of Fli1^CTA/CTA mice maintained elevated synthesis of collagen mRNA and protein. Additional experiments in cultured fibroblasts have revealed that although Fli1 CTA retains the ability to bind to the collagen promoter in vitro and in vivo, it no longer functions as transcriptional repressor. Together, these results establish Fli1 as a key regulator of the collagen homeostasis in the skin in vivo.

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* Corresponding author. Mailing address: Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC 29425. Phone: (843) 792-7921. Fax: (843) 792-7121. E-mail: trojanme{at}musc.edu

Published ahead of print on 10 November 2008.

Y.A. and M.M. contributed equally to this work.

Present address: Department of Dermatology, Tokyo Kosei-Nenkin Hospital, 5-1 Tsukudo-cho, Shinjuku-ku, Tokyo 162-8543, Japan.

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Molecular and Cellular Biology, January 2009, p. 425-434, Vol. 29, No. 2
0270-7306/09/$08.00+0     doi:10.1128/MCB.01278-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

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