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Sci Transl Med. 2018 Jul 25;10(451). pii: eaap8798. doi: 10.1126/scitranslmed.aap8798.

Transcriptional signature primes human oral mucosa for rapid wound healing.

Author information

1
Laboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA.
2
Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD 20892, USA.
3
Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
4
Oral Immunity and Inflammation Unit, National Institute of Dental and Craniofacial Research, Bethesda, MD 20892, USA.
5
Biodata Mining and Discovery Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA.
6
Moores Cancer Center, University California, San Diego, La Jolla, CA 92093, USA.
7
Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD 20892, USA. morasso@nih.gov sgutkind@ucsd.edu.
8
Laboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA. morasso@nih.gov sgutkind@ucsd.edu.

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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