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Oral versus Skin Mucosa Comparison Provides New Targets to Enhance Wound Healing

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Review of "Transcriptional signature primes human oral mucosa for rapid wound healing" from Science Translational Medicine by Stuart P. Atkinson

Enhanced wound healing currently represents a major medical and social priority, and as oral (and embryonic) wound healing occurs at a more rapid pace in a scar-free manner when compared to skin wound healing [1-3], the dissection of the molecular mechanisms at play may permit the generation of new and improved strategies.

To this end, researchers from the laboratories of J. Silvio Gutkind (UCSD, La Jolla, CA, USA) and Maria I. Morasso (NIAMS, Bethesda, MD, USA) compared the transcriptional profiles of healthy human oral mucosa and skin biopsies under normal conditions and during wound healing. Reporting in Science Translational Medicine, Iglesias-Bartolome et al. now establish that the exploitation of gene networks active in oral mucosa keratinocytes that limit differentiation and proinflammatory responses may accelerate wound repair in the skin [4].

The authors first discovered, as expected, that oral wounds resolved significantly faster than skin wounds, and initial analyses suggested that the normal unwounded oral epithelium already displayed a transcriptional profile similar to wounded skin, evidenced by the expression of wound-activated networks. In short, the oral mucosa is "primed" at all times, ready to affect wound repair and inflammatory control, whereas the skin is not. Additionally, the study observed that the oral wound healing process involved the upregulation of gene networks that control epithelial cell differentiation and regulate proinflammatory responses.

The data also implied that keratinocytes drove many of the critical wound healing processes, and subsequent analysis identified SOX2 (sex-determining region Y-box 2) and PITX1 (paired-like homeodomain 1) as two crucial transcriptional regulators of the wound healing process present in oral keratinocytes when compared to those from the skin. However, the forced expression of SOX2 and PITX1 in skin keratinocytes permitted enhanced repair in a mouse model of wound healing, suggesting an innovative means to provide improved wound healing properties to a non-oral tissue.

The authors believe their findings will have widespread implications for the wound healing field, as the gene and networks involved may help to develop novel therapies that promote rapid and scarless healing and aid the treatment of chronic and non-healing wounds.

For more on all the advances in wound healing, stay tuned to the Stem Cells Portal.

References

  1. Sciubba JJ, Waterhouse JP, and Meyer J, A fine structural comparison of the healing of incisional wounds of mucosa and skin. J Oral Pathol 1978;7:214-27.
  2. Szpaderska AM, Zuckerman JD, and DiPietro LA, Differential injury responses in oral mucosal and cutaneous wounds. J Dent Res 2003;82:621-6.
  3. Turabelidze A, Guo S, Chung AY, et al., Intrinsic Differences between Oral and Skin Keratinocytes. PLOS ONE 2014;9:e101480.
  4. Iglesias-Bartolome R, Uchiyama A, Molinolo AA, et al., Transcriptional signature primes human oral mucosa for rapid wound healing. Science Translational Medicine 2018;10.