Epithelial regulation of mesenchymal tissue behavior

Corrie L. Gallant-Behm, Pan Du, Simon M. Lin, Phillip Marucha, Luisa A. Dipietro, Thomas A. Mustoe

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Fibroproliferative scars are an important clinical problem, and yet the mechanisms that regulate scar formation remain poorly understood. This study explored the hypothesis that the epithelium has a critical role in dictating scar formation, and that these interactions differ in skin and mucosa. Paired skin and vaginal mucosal wounds on New Zealand white (NZW) rabbits diverged significantly; the cutaneous epithelium exhibited a greater and prolonged response to injury when compared with the mucosa. Microarray analysis of the injured epithelium was performed, and numerous factors were identified that were more strongly upregulated in skin, including several proinflammatory cytokines and profibrotic growth factors. Analysis of the underlying mesenchymal tissue demonstrated a fibrotic response in the dermis of the skin but not the mucosal lamina propria, in the absence of a connective tissue injury. To determine if the proinflammatory factors produced by the epidermis may have a role in dermal fibrosis, an IL-1 receptor antagonist was administered locally to healing skin wounds. In the NZW rabbit model, blockade of IL-1 signaling was effective in preventing hypertrophic scar formation. These results support the idea that soluble factors produced by the epithelium in response to injury may influence fibroblast behavior and regulate scar formation in vivo.

Original languageEnglish (US)
Pages (from-to)892-899
Number of pages8
JournalJournal of Investigative Dermatology
Volume131
Issue number4
DOIs
StatePublished - Apr 2011
Externally publishedYes

Fingerprint

Skin
Tissue
Cicatrix
Epithelium
Mucous Membrane
Wounds and Injuries
Interleukin-1 Receptors
Fibroblasts
Microarrays
Interleukin-1
Rabbits
Hypertrophic Cicatrix
Intercellular Signaling Peptides and Proteins
Microarray Analysis
Dermis
Epidermis
Cytokines
Connective Tissue
Wound Healing
Fibrosis

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Gallant-Behm, C. L., Du, P., Lin, S. M., Marucha, P., Dipietro, L. A., & Mustoe, T. A. (2011). Epithelial regulation of mesenchymal tissue behavior. Journal of Investigative Dermatology, 131(4), 892-899. https://doi.org/10.1038/jid.2010.420

Epithelial regulation of mesenchymal tissue behavior. / Gallant-Behm, Corrie L.; Du, Pan; Lin, Simon M.; Marucha, Phillip; Dipietro, Luisa A.; Mustoe, Thomas A.

In: Journal of Investigative Dermatology, Vol. 131, No. 4, 04.2011, p. 892-899.

Research output: Contribution to journalArticle

Gallant-Behm, CL, Du, P, Lin, SM, Marucha, P, Dipietro, LA & Mustoe, TA 2011, 'Epithelial regulation of mesenchymal tissue behavior', Journal of Investigative Dermatology, vol. 131, no. 4, pp. 892-899. https://doi.org/10.1038/jid.2010.420
Gallant-Behm, Corrie L. ; Du, Pan ; Lin, Simon M. ; Marucha, Phillip ; Dipietro, Luisa A. ; Mustoe, Thomas A. / Epithelial regulation of mesenchymal tissue behavior. In: Journal of Investigative Dermatology. 2011 ; Vol. 131, No. 4. pp. 892-899.
@article{91dcb83587b54269a8e5f1b2df59e567,
title = "Epithelial regulation of mesenchymal tissue behavior",
abstract = "Fibroproliferative scars are an important clinical problem, and yet the mechanisms that regulate scar formation remain poorly understood. This study explored the hypothesis that the epithelium has a critical role in dictating scar formation, and that these interactions differ in skin and mucosa. Paired skin and vaginal mucosal wounds on New Zealand white (NZW) rabbits diverged significantly; the cutaneous epithelium exhibited a greater and prolonged response to injury when compared with the mucosa. Microarray analysis of the injured epithelium was performed, and numerous factors were identified that were more strongly upregulated in skin, including several proinflammatory cytokines and profibrotic growth factors. Analysis of the underlying mesenchymal tissue demonstrated a fibrotic response in the dermis of the skin but not the mucosal lamina propria, in the absence of a connective tissue injury. To determine if the proinflammatory factors produced by the epidermis may have a role in dermal fibrosis, an IL-1 receptor antagonist was administered locally to healing skin wounds. In the NZW rabbit model, blockade of IL-1 signaling was effective in preventing hypertrophic scar formation. These results support the idea that soluble factors produced by the epithelium in response to injury may influence fibroblast behavior and regulate scar formation in vivo.",
author = "Gallant-Behm, {Corrie L.} and Pan Du and Lin, {Simon M.} and Phillip Marucha and Dipietro, {Luisa A.} and Mustoe, {Thomas A.}",
year = "2011",
month = "4",
doi = "10.1038/jid.2010.420",
language = "English (US)",
volume = "131",
pages = "892--899",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Epithelial regulation of mesenchymal tissue behavior

AU - Gallant-Behm, Corrie L.

AU - Du, Pan

AU - Lin, Simon M.

AU - Marucha, Phillip

AU - Dipietro, Luisa A.

AU - Mustoe, Thomas A.

PY - 2011/4

Y1 - 2011/4

N2 - Fibroproliferative scars are an important clinical problem, and yet the mechanisms that regulate scar formation remain poorly understood. This study explored the hypothesis that the epithelium has a critical role in dictating scar formation, and that these interactions differ in skin and mucosa. Paired skin and vaginal mucosal wounds on New Zealand white (NZW) rabbits diverged significantly; the cutaneous epithelium exhibited a greater and prolonged response to injury when compared with the mucosa. Microarray analysis of the injured epithelium was performed, and numerous factors were identified that were more strongly upregulated in skin, including several proinflammatory cytokines and profibrotic growth factors. Analysis of the underlying mesenchymal tissue demonstrated a fibrotic response in the dermis of the skin but not the mucosal lamina propria, in the absence of a connective tissue injury. To determine if the proinflammatory factors produced by the epidermis may have a role in dermal fibrosis, an IL-1 receptor antagonist was administered locally to healing skin wounds. In the NZW rabbit model, blockade of IL-1 signaling was effective in preventing hypertrophic scar formation. These results support the idea that soluble factors produced by the epithelium in response to injury may influence fibroblast behavior and regulate scar formation in vivo.

AB - Fibroproliferative scars are an important clinical problem, and yet the mechanisms that regulate scar formation remain poorly understood. This study explored the hypothesis that the epithelium has a critical role in dictating scar formation, and that these interactions differ in skin and mucosa. Paired skin and vaginal mucosal wounds on New Zealand white (NZW) rabbits diverged significantly; the cutaneous epithelium exhibited a greater and prolonged response to injury when compared with the mucosa. Microarray analysis of the injured epithelium was performed, and numerous factors were identified that were more strongly upregulated in skin, including several proinflammatory cytokines and profibrotic growth factors. Analysis of the underlying mesenchymal tissue demonstrated a fibrotic response in the dermis of the skin but not the mucosal lamina propria, in the absence of a connective tissue injury. To determine if the proinflammatory factors produced by the epidermis may have a role in dermal fibrosis, an IL-1 receptor antagonist was administered locally to healing skin wounds. In the NZW rabbit model, blockade of IL-1 signaling was effective in preventing hypertrophic scar formation. These results support the idea that soluble factors produced by the epithelium in response to injury may influence fibroblast behavior and regulate scar formation in vivo.

UR - http://www.scopus.com/inward/record.url?scp=79952765433&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952765433&partnerID=8YFLogxK

U2 - 10.1038/jid.2010.420

DO - 10.1038/jid.2010.420

M3 - Article

C2 - 21228814

AN - SCOPUS:79952765433

VL - 131

SP - 892

EP - 899

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 4

ER -