Research ArticleWound Healing

Transcriptional signature primes human oral mucosa for rapid wound healing

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Science Translational Medicine  25 Jul 2018:
Vol. 10, Issue 451, eaap8798
DOI: 10.1126/scitranslmed.aap8798

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Rapid repair

Wounds in the mouth heal faster and with less scarring than wounds in other locations on the body. To understand differences in healing, Iglesias-Bartolome et al. performed transcriptional analysis on sequential, paired oral and skin biopsies from healthy human subjects. Compared to baseline, skin samples showed a larger number of up-regulated genes on subsequent biopsies than oral samples, indicating that healing was unresolved. Oral wounds healed faster than skin wounds, and certain transcription factors were consistently up-regulated in the oral wounds but not in skin wounds. Overexpressing some of these transcription factors in a mouse model of skin wounding enhanced healing. The authors suggest that the molecular signature of the oral mucosa could be used to develop therapies for wound healing.

Abstract

Oral mucosal wound healing has long been regarded as an ideal system of wound resolution. However, the intrinsic characteristics that mediate optimal healing at mucosal surfaces are poorly understood, particularly in humans. We present a unique comparative analysis between human oral and cutaneous wound healing using paired and sequential biopsies during the repair process. Using molecular profiling, we determined that wound-activated transcriptional networks are present at basal state in the oral mucosa, priming the epithelium for wound repair. We show that oral mucosal wound–related networks control epithelial cell differentiation and regulate inflammatory responses, highlighting fundamental global mechanisms of repair and inflammatory responses in humans. The paired comparative analysis allowed for the identification of differentially expressed SOX2 (sex-determining region Y-box 2) and PITX1 (paired-like homeodomain 1) transcriptional regulators in oral versus skin keratinocytes, conferring a unique identity to oral keratinocytes. We show that SOX2 and PITX1 transcriptional function has the potential to reprogram skin keratinocytes to increase cell migration and improve wound resolution in vivo. Our data provide insights into therapeutic targeting of chronic and nonhealing wounds based on greater understanding of the biology of healing in human mucosal and cutaneous environments.

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