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Originally published In Press as doi:10.1074/jbc.M309616200 on October 3, 2003

J. Biol. Chem., Vol. 278, Issue 51, 51527-51534, December 19, 2003
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Oral Fibroblast Expression of wound-inducible transcript 3.0 (wit3.0) Accelerates the Collagen Gel Contraction in Vitro*

Cortino Sukotjo{ddagger}, Audrey Lin{ddagger}§, Kevin Song{ddagger}§, Takahiro Ogawa{ddagger}, Ben Wu{ddagger}§, and Ichiro Nishimura{ddagger}||

From the {ddagger}The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry, UCLA School of Dentistry, Los Angeles, California 90095-1668 and the Departments of §Bioengineering and Materials Science and Engineering, UCLA Henry Samueli School of Engineering and Applied Science, Los Angeles, California 90095-1595

Wounds of the oral mucosa show faster closure with less scar formation than skin wounds in other areas. A differentially expressed cDNA, wound-inducible transcript 3.0 (wit3.0), was isolated from oral mucosal wound in rats (Sukotjo, C., Abanmy, A. A., Ogawa, T., and Nishimura, I. (2002) J. Dent. Res. 81, 229–235). The purpose of this study was to characterize the wit3.0 gene structure and the function of its deduced peptide. Human and rat genome databases revealed that the gene for wit3.0 was located in human chromosome 12p11.23 and rat chromosome 4q44. Its human and rat gene structures were well conserved, composed of 7 exons spread over 20 kb. Exon 5 was alternatively spliced generating two transcripts encoding deduced peptides of 215 and 253 amino acids (wit3.0{alpha} and wit3.0{beta}, respectively). The protein families data base of alignments (Pfam) analysis suggested the wit3.0 peptide sequence shared similarity with a portion of the myosin II coiled-coil domain consensus sequence. Fibroblasts isolated from the rat oral wound up-regulated wit3.0 expression and exhibited greater ability to contract collagen gel in vitro than fibroblasts isolated from untreated oral mucosa/gingiva. NIH3T3 and rat oral fibroblasts transfected with expression vector containing the coding sequences of wit3.0{alpha} or wit3.0{beta} increased in vitro collagen gel contraction. When treated with TGF{beta}-1, NIH3T3 fibroblast expression of wit3.0 showed no significant change, whereas alpha smooth muscle actin was increased in a dose-dependent manner. These data suggest that there may be a novel wound healing pathway involving wit3.0 underlying the favorable early wound closure characteristics of oral mucosa.


Received for publication, August 29, 2003 , and in revised form, September 23, 2003.

* This work was supported by the UCLA Academic Senate Faculty Grant Program (to I. N.) and a Procter & Gamble ACP Fellowship (to C. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

|| To whom correspondence should be addressed: The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, Box 951668, CHS B3–087, Los Angeles, CA 90095-1668. Tel.: 310-794-7612; Fax: 310-825-6345; E-mail: ichiron{at}dent.ucla.edu.


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H.E. van Beurden, J.W. Von den Hoff, R. Torensma, J.C. Maltha, and A.M. Kuijpers-Jagtman
Myofibroblasts in Palatal Wound Healing: Prospects for the Reduction of Wound Contraction after Cleft Palate Repair
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