Expression of apoptosis-associated genes by human dermal scar fibroblasts

Authors

  • Diana V. Messadi BDS, DMSc,

    1. From the School of Dentistrya, and Dental Research Instituteb, University of California Los Angeles, Charles R. Drew University of Medicine and Sciencesc, Los Angeles, and School of Dentistry, University of California San Francisco, California
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  • a,b Anh Le DDS, Phd,

    1. From the School of Dentistrya, and Dental Research Instituteb, University of California Los Angeles, Charles R. Drew University of Medicine and Sciencesc, Los Angeles, and School of Dentistry, University of California San Francisco, California
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  • a Steve Berg BS,

    1. From the School of Dentistrya, and Dental Research Instituteb, University of California Los Angeles, Charles R. Drew University of Medicine and Sciencesc, Los Angeles, and School of Dentistry, University of California San Francisco, California
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  • a Anahid Jewett Phd,

    1. From the School of Dentistrya, and Dental Research Instituteb, University of California Los Angeles, Charles R. Drew University of Medicine and Sciencesc, Los Angeles, and School of Dentistry, University of California San Francisco, California
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  • a,b Zhuang Wen DDS,

    1. From the School of Dentistrya, and Dental Research Instituteb, University of California Los Angeles, Charles R. Drew University of Medicine and Sciencesc, Los Angeles, and School of Dentistry, University of California San Francisco, California
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  • a Paul Kelly MD,

    1. From the School of Dentistrya, and Dental Research Instituteb, University of California Los Angeles, Charles R. Drew University of Medicine and Sciencesc, Los Angeles, and School of Dentistry, University of California San Francisco, California
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  • and c Charles N. Bertolami DDS, DMSc d

    1. From the School of Dentistrya, and Dental Research Instituteb, University of California Los Angeles, Charles R. Drew University of Medicine and Sciencesc, Los Angeles, and School of Dentistry, University of California San Francisco, California
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Abstract

The purpose of this study was to determine if aberrant apoptosis plays a role in pathologic wound healing as manifested by hypertrophic scarring and keloid formation. Apoptosis has recently been found to participate in the transition between granulation tissue and the development of definitive scar. The question that remains to be answered is what stimuli initiate apoptosis during wound healing. Hitherto, regulatory factors and pathways involved have been largely undefined. We investigated heterogeneity among fibroblasts derived from normal skin and keloid scar, by examining apoptotic profiles and pathways for these cells. Quantitative analysis of apoptotic cells using an Annexin-V-FITC binding assay showed that normal skin fibroblast cultures were found to have a two-fold higher percentage of apoptotic cells than did keloid fibroblast cultures. To study apoptotic pathways and related death-associated genes, a ribonuclease protection assay was performed for fibroblasts exposed to anti-Fas antibody and tumor necrosis factor-α to activate the Fas/TNF receptor apoptotic pathway. Compared with normal skin fibroblasts, keloid fibroblasts exhibited decreased expression of apoptosis-associated genes.

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