May 2005
Volume 46, Issue 13
ARVO Annual Meeting Abstract  |   May 2005
c–Jun Activates Wound Healing–Associated Gene Promoters and Is Transcriptionally Regulated By Thymosin ß 4 (Tß4) in Human Cornea Epithelial Cells
Author Affiliations & Notes
  • P. Qiu
    Ophthalmology, Wayne State University, Detroit, MI
  • G. Sosne
    Ophthalmology, Wayne State University, Detroit, MI
  • Footnotes
    Commercial Relationships  P. Qiu, None; G. Sosne, None.
  • Footnotes
    Support  NIH EY 13412, Research to Prevent Blindness
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 2143. doi:
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      P. Qiu, G. Sosne; c–Jun Activates Wound Healing–Associated Gene Promoters and Is Transcriptionally Regulated By Thymosin ß 4 (Tß4) in Human Cornea Epithelial Cells . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2143.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract: : Purpose:This study investigated the c–Jun mediated transcriptional regulation of wound–healing related genes and the potential modulation of c–Jun expression by Tß4 in human cornea epithelial cells. Methods: Transient transfection was performed in cultured human cornea epithelial cells (HCET) with vectors expressing wild type and mutants of c–Jun and luciferase–reporters driven by the promoter for the transcription of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), plasminogen activator inhibitor type–1 (PAI–1) and laminin–5 (LM–5). The effects of different signaling pathways were analyzed during c–Jun mediated promoter activation. The dynamics of c–Jun mRNA and protein levels were assayed in Tß4–treated HCET. In addition, Tß4–promotion of cell migration was evaluated in an in vitro scrape wound model. Results: Overexpression of c–Jun, but not c–Fos, increased MMP–1 and LM–5’s promoter activity 30 and 10 fold respectively. This stimulatory function depends on both c–Jun’s domains for DNA binding, dimerization and transcriptional activation and cis–elements in the promoter regions for AP–1 binding. The c–jun mediated promoter activation was partially blocked by SP600, an inhibitor for the JNK pathway, and overpression of the dominant negative type of c–Fos. c–Jun mildly enhanced MMP–9 and PAI–1 promoter activity. c–Jun’s dominant negative elevated TIMP–1 promoter activity. Tß4 promoted migration of cultured HCET and transiently stimulated c–Jun expression at least 2 fold at 30 minutes and 1 hour after treatment. Conclusions: In HCET, overexpression of c–Jun dramatically increases MMP–1 and LM–5 promoter activation. C–Jun’s function involves direct binding to the promoter’s targeted region, forming hetero– and homodimer, and JNK’s phosphorylation. Tß4 promotes cell migration during wound healing and increases c–Jun expression. Our data suggests that Tß4 may promote epithelial cell migration through c–Jun mediated gene expression.

Keywords: cornea: epithelium • transcription factors • wound healing 

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