Transcriptional signature primes human oral mucosa for rapid wound healing.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Iglesias-Bartolome, R; Uchiyama, A; Molinolo, AA; Abusleme, L; Brooks, SR; Callejas-Valera, JL; Edwards, D; Doci, C; Asselin-Labat, M-L; Onaitis, MW; Moutsopoulos, NM; Gutkind, JS; Morasso, MI

Published Date

  • July 25, 2018

Published In

Volume / Issue

  • 10 / 451

PubMed ID

  • 30045979

Pubmed Central ID

  • 30045979

Electronic International Standard Serial Number (EISSN)

  • 1946-6242

Digital Object Identifier (DOI)

  • 10.1126/scitranslmed.aap8798

Language

  • eng

Conference Location

  • United States