Downregulation of Apoptosis-Related Genes in Keloid Tissues

doi:10.1006/jsre.1999.5761

Journal of Surgical Research

Volume 87, Issue 2, December 1999, Pages 209-216

https://doi.org/10.1006/jsre.1999.5761 Get rights and content

Abstract

Background. Physiologically programmed cell death or apoptosis occurs during the natural balance between cellular proliferation and demise.

Materials and Methods. We compared the expression of 64 apoptosis-related genes in keloids and normal scars to investigate the potential role of apoptosis in keloid formation. Two sets of mRNA were isolated from keloids excised from four previously untreated patients and four normal scar patients separately. Human cDNA arrayed hybridization was performed to compare the apoptosis-related gene expression between these two groups. In addition, TUNEL assays were performed to evaluate the percentage of apoptotic cells in keloids (center and periphery) versus normal scars.

Results. Eight of the sixty-four apoptosis-related genes studied were significantly underexpressed in keloid tissue. The underexpressed genes and their relative expression compared with normal scar were defender against cell death 1 (DAD-1) (34.1% of normal scar); nucleoside diphosphate kinase B (c-myc transcription factor) (24.7%); glutathione S-transferase (17.9%); glutathione S-transferase microsomal (28.1%); glutathione peroxidase (47.2%); tumor necrosis factor receptor 1-associated protein (TRADD) (51.0%); 19-kDa interacting protein 3 (NIP3) (36.0%); and cytoplasmic dynein light chain 1 (HDLC1) (47.7%). Spatial analysis of apoptosis using TUNEL assays revealed apoptosis indices of 0.83 for keloid periphery and 0.63 for keloid center.

Conclusions. In this study we demonstrated underexpression of apoptosis-related genes in human keloid tissue and decreased apoptotic activity in fibroblasts derived from keloids versus normal scars. We hypothesized that keloid fibroblasts fail to undergo physiologically programmed cell death and, thus, continue to produce and secrete connective tissue beyond the period expected in normal scar formation, accounting for the progressive and hypertrophic nature of keloids. This mechanism leads to new possibilities for treatment of keloids through induction of apoptosis.

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^☆: Supported by a Wunderman Family Foundation grant, a UCLA Dental Research Institute opportunity grant, OMSF Grant 014741, NIH/NIDR Grant DE94001, and CRC/NIH Grant RR00865.

²: Both Dr. Ting and Dr. Zhang serve as the senior authors.

³: To whom correspondence should be addressed at UCLA School of Dentistry, 10833 Le Conte Avenue, CHS 30-113, Los Angeles, CA 90095. Fax: (310) 206–5349. E-mail: [email protected].

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Regular ArticleDownregulation of Apoptosis-Related Genes in Keloid Tissues☆

Abstract

Dermatol. Clin.

Int. Rev. Cytol.

Anal. Biochem.

J. Am. Acad. Dermatol.

J. Biol. Biochem.

Cell

Cell

FEBS Lett.

Biochem. Pharmacol.

Surgery

J. Surg. Res.

Cell Biol. Int.

Curr. Opin. Cell Biol.

Cell

Trends Biochem. Sci.

Keloids in various races: A review of 175 cases

Plast. Reconstr. Surg.

Apoptosis, necrosis, and proliferation: Possible implications in the etiology of keloids

Am. J. Pathol.

Reduced growth-factor requirement of keloid-derived fibroblasts may account for tumor growth

Proc. Natl. Acad. Sci. USA

Elevated levels of PDGF-alpha receptors in keloid fibroblasts contribute to an enhanced response to PDGF

J. Invest. Dermatol.

Excessive scarring as a consequence of healing

Wound Repair Regeneration

Keloids and hypertrophic scars

J. Dermatol. Surg. Oncol.

Necrosis and apoptosis: Distinct modes of cell death with fundamentally different significance

Pathol. Annu.

Cell death by apoptosis and its protective role against disease

Trends Pharmacol. Sci.

Regular Article
Downregulation of Apoptosis-Related Genes in Keloid Tissues☆