Transcriptional signature primes human oral mucosa for rapid wound healing

Ramiro Iglesias-Bartolome, Akihiko Uchiyama, Alfredo A. Molinolo, Loreto Abusleme, Stephen R. Brooks, Juan Luis Callejas-Valera, Dean Edwards, Colleen Doci, Marie-Liesse Labat, Mark W. Onaitis, Niki M. Moutsopoulos, J. Silvio Gutkind, Maria I. Morasso

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbereaap8798
JournalScience Translational Medicine
Volume10
Issue number451
DOIs
StatePublished - Jul 25 2018
Externally publishedYes

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Mouth Mucosa
Wound Healing
Wounds and Injuries
Keratinocytes
Skin
Gene Regulatory Networks
Cell Movement
Cell Differentiation
Epithelium
Epithelial Cells
Biopsy

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Iglesias-Bartolome, R., Uchiyama, A., Molinolo, A. A., Abusleme, L., Brooks, S. R., Callejas-Valera, J. L., ... Morasso, M. I. (2018). Transcriptional signature primes human oral mucosa for rapid wound healing. Science Translational Medicine, 10(451), [eaap8798]. https://doi.org/10.1126/scitranslmed.aap8798

Transcriptional signature primes human oral mucosa for rapid wound healing. / Iglesias-Bartolome, Ramiro; Uchiyama, Akihiko; Molinolo, Alfredo A.; Abusleme, Loreto; Brooks, Stephen R.; Callejas-Valera, Juan Luis; Edwards, Dean; Doci, Colleen; Labat, Marie-Liesse; Onaitis, Mark W.; Moutsopoulos, Niki M.; Silvio Gutkind, J.; Morasso, Maria I.

In: Science Translational Medicine, Vol. 10, No. 451, eaap8798, 25.07.2018.

Research output: Contribution to journalArticle

Iglesias-Bartolome, R, Uchiyama, A, Molinolo, AA, Abusleme, L, Brooks, SR, Callejas-Valera, JL, Edwards, D, Doci, C, Labat, M-L, Onaitis, MW, Moutsopoulos, NM, Silvio Gutkind, J & Morasso, MI 2018, 'Transcriptional signature primes human oral mucosa for rapid wound healing', Science Translational Medicine, vol. 10, no. 451, eaap8798. https://doi.org/10.1126/scitranslmed.aap8798
Iglesias-Bartolome R, Uchiyama A, Molinolo AA, Abusleme L, Brooks SR, Callejas-Valera JL et al. Transcriptional signature primes human oral mucosa for rapid wound healing. Science Translational Medicine. 2018 Jul 25;10(451). eaap8798. https://doi.org/10.1126/scitranslmed.aap8798
Iglesias-Bartolome, Ramiro ; Uchiyama, Akihiko ; Molinolo, Alfredo A. ; Abusleme, Loreto ; Brooks, Stephen R. ; Callejas-Valera, Juan Luis ; Edwards, Dean ; Doci, Colleen ; Labat, Marie-Liesse ; Onaitis, Mark W. ; Moutsopoulos, Niki M. ; Silvio Gutkind, J. ; Morasso, Maria I. / Transcriptional signature primes human oral mucosa for rapid wound healing. In: Science Translational Medicine. 2018 ; Vol. 10, No. 451.
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