Human skin culture as an ex vivo model for assessing the fibrotic effects of insulin-like growth factor binding proteins

Hidekata Yasuoka, Adriana T. Larregina, Yukie Yamaguchi, Carol A. Feghali-Bostwick

Research output: Contribution to journalArticle

Abstract

Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology. A hallmark of SSc is fibrosis of the skin and internal organs. We recently demonstrated increased expression of IGFBP-3 and IGFBP-5 in primary cultures of fibroblasts from the skin of patients with SSc. In vitro, IGFBP-3 and IGFBP-5 induced a fibrotic phenotype and IGFBP-5 triggered dermal fibrosis in mice. To assess the ability of IGFBPs to trigger fibrosis, we used an ex vivo human skin organ culture model. Our findings demonstrate that IGFBP-3 and IGFBP-5, but not IGFBP-4, increase dermal and collagen bundle thickness in human skin explants, resulting in substantial dermal fibrosis and thickening. These fibrotic effects were sustained for at least two weeks. Our findings demonstrate that human skin ex vivo is an appropriate model to assess the effects of fibrosis-inducing factors such as IGFBPs, and for evaluating the efficacy of inhibitors/therapies to halt the progression of fibrosis and potentially reverse it.

Original languageEnglish
Pages (from-to)17-22
Number of pages6
JournalThe open rheumatology journal
Volume2
DOIs
Publication statusPublished - 2008 Jan 1

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Insulin-Like Growth Factor Binding Proteins
Insulin-Like Growth Factor Binding Protein 5
Skin
Fibrosis
Insulin-Like Growth Factor Binding Protein 3
Systemic Scleroderma
Insulin-Like Growth Factor Binding Protein 4
Connective Tissue Diseases
Organ Culture Techniques
Collagen
Fibroblasts
Phenotype

ASJC Scopus subject areas

  • Rheumatology

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Human skin culture as an ex vivo model for assessing the fibrotic effects of insulin-like growth factor binding proteins. / Yasuoka, Hidekata; Larregina, Adriana T.; Yamaguchi, Yukie; Feghali-Bostwick, Carol A.

In: The open rheumatology journal, Vol. 2, 01.01.2008, p. 17-22.

Research output: Contribution to journalArticle

Yasuoka, Hidekata ; Larregina, Adriana T. ; Yamaguchi, Yukie ; Feghali-Bostwick, Carol A. / Human skin culture as an ex vivo model for assessing the fibrotic effects of insulin-like growth factor binding proteins. In: The open rheumatology journal. 2008 ; Vol. 2. pp. 17-22.
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