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Ha-Sheng Li, MD, PhD; Patricia A. Hebda, PhD; Lori A. Kelly, BS; Garth D. Ehrlich, PhD; David C. Whitcomb, MD, PhD; Joseph E. Dohar, MD, MS

Arch Otolaryngol Head Neck Surg. 2000;126:1337-1343.

Background  Scar formation and subglottic stenosis often cause health problems in surgical otolaryngology. However, fetal wounds demonstrate scarless healing. The underlying mechanism remains poorly understood. We isolated differentially expressed genes by comparison between nonwounded with wounded skin of fetal and adult rabbits.

Methods  Skin incisional wounds were made in fetal (21 to 23 days' gestation) and adult rabbits. Nonwounded and wounded skin were harvested 12 hours after surgery. Total RNA was extracted. By means of messenger RNA differential display, differentially expressed complementary DNA fragments were isolated, cloned, and sequenced. The expressed transcripts were verified by reverse RNA dot blot and semiquantitative reverse transcription and polymerase chain reaction.

Results  One complementary DNA tag that was induced in fetal skin wounds and repressed in adult skin wounds was isolated. The sequence of this complementary DNA (352 base pairs) encodes the messenger RNA for the E-prostanoid (EP) 4 receptor for prostaglandin E₂ (PGE₂). The truly differential expression of the transcript was confirmed. In normal skin, the EP4 receptor messenger RNA levels were higher in adults than in fetuses. Twelve hours after wounding, the EP4 receptor transcript was remarkably induced in fetal skin wounds but repressed in adult skin wounds.

Conclusions  Our study demonstrates the differential expression of the EP4 receptor messenger RNA in fetal and adult skin before and 12 hours after wounding. Our results suggest that prostaglandin E₂ is involved in the differential cellular responses and in the regulation of the intracellular signal transduction through its binding to EP4 receptor during fetal wound repair.

From the Departments of Otolaryngology (Drs Li, Hebda, and Dohar), Medicine (Drs Li and Whitcomb), and Cell Biology and Molecular Physiology (Drs Hebda and Whitcomb) and Center for Genomic Sciences (Drs Li and Whitcomb), University of Pittsburgh School of Medicine, Pittsburgh, Pa; ENT Wound Healing Research Program, Department of Pediatric Otolaryngology, Children's Hospital of Pittsburgh (Drs Hebda and Dohar and Ms Kelly); and Center for Genomic Sciences, Allegheny General Hospital, Pittsburgh (Dr Ehrlich).

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