Elevated expression of type VII collagen in the skin of patients with systemic sclerosis. Regulation by transforming growth factor-β

L. Rudnicka, J. Varga, A. M. Christiano, R. V. Iozzo, S. A. Jimenez, J. Uitto*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

A hallmark of systemic sclerosis (SSc) is the development of tissue fibrosis. Excessive production of several connective tissue components normally present in the dermis, including type I, III, V, and VI collagens as well as fibronectin and proteoglycans, is a consistent finding in the skin of SSc patients. Type VII collagen is a major constituent of anchoring fibrils, present in the skin at the dermal-epidermal basement membrane zone. TGF-β has been shown to upregulate the expression of the type VII collagen gene. In this study, we assessed the expression of type VII collagen and TGF-β in the skin of patients with SSc. Indirect immunofluorescence showed an abundance of type VII collagen in the patients' skin, including the dermis. Ultrastructural analysis of SSc skin revealed an abundance of fibrillar material, possibly representing type VII collagen. The increased expression of type VII collagen epitopes was accompanied by the elevated expression of immunodetectable TGF-β1 and TGF-β2. Dermal fibroblasts cultured from the affected individuals showed a statistically significant (P < 0.02) increase in the expression of type VII collagen at the mRNA level, as detected by reverse transcription-PCR with a mutated cDNA as an internal standard, and increased deposition of the protein as assessed by indirect immunofluorescence. Thus, type VII collagen is abundantly present in SSc patients' dermis, a location not characteristic of its normal distribution, and its aberrant expression may relate to the presence of TGF-β in the same topographic distribution. The presence of type VII collagen in the dermis may contribute to the tightly bound and indurated appearance of the affected skin in SSc patients.

Original languageEnglish (US)
Pages (from-to)1709-1715
Number of pages7
JournalJournal of Clinical Investigation
Volume93
Issue number4
DOIs
StatePublished - 1994

Keywords

  • anchoring fibrils
  • systemic sclerosis
  • tissue fibrosis
  • transforming growth factor-β
  • type VII collagen

ASJC Scopus subject areas

  • Medicine(all)

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