Diminished transforming growth factor β2 production leads to increased expression of a profibrotic procollagen α2 type I messenger RNA variant in embryonic fibroblasts of UCD-200 chickens, a model for systemic sclerosis

Martina Prelog, Paul Scheidegger, Silvia Peter, M. Eric Gershwin, Georg Wick, Roswitha Sgonc

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Objective. A procollagen α2(I) messenger RNA (mRNA) variant, with a 115-bp band and an expected band of 180 bp, was found to be increased during early, acute scleroderma-like disease in UCD-200 chickens. The present study investigated the influence of cytokines on the expression of these 2 proα2(I) mRNA variants. Methods. Embryonic fibroblasts of UCD-200 chickens (UCD-200-CEF) and normal white leghorns (NWL-CEF) were grown in 3-dimensional collagen gels. Procollagen mRNA expression was analyzed by RNase protection assay, and proliferation was determined by 3H-thymidine incorporation. Transforming growth factor β1 (TGFβ1) and TGFβ2 were measured in culture supernatants by enzyme-linked immunosorbent assay. Results. Compared with NWL-CEF, UCD-200-CEF expressed 7.2 times more of the smaller profibrotic proα2(I) mRNA variant. TGFβ1 stimulated the proliferation of UCD-200-CEF, but not NWL-CEF. The 115 bp:180 bp ratio was increased by TGFβ1 in both NWL-CEF and UCD-CEF. TGFβ2 and TGFβ3 reduced the expression of the profibrotic proα2(I) mRNA in UCD-200-CEF to the same levels observed in healthy control NWL-CEF. In culture supernatants, NWL-CEF produced 4.1 times more TGFβ2 than that produced by UCD-CEF. Inhibition of endogenous TGFβ2 in NWL-CEF resulted in the same 115 bp:180 bp ratio as seen in untreated UCD-CEF. Conclusion. TGFβ2 reduces the expression of a profibrotic proα2(I) mRNA variant in UCD-200-CEF. The constitutive overproduction of this proα2(I) mRNA variant and the diminished synthesis of TGFβ2 in untreated UCD-200-CEF suggest that TGFβ2 can act as an antifibrotic cytokine and might be a key player during fibrosis onset. These results shed light on the contradictory observations regarding the role of TGFβ2 in human systemic sclerosis.

Original languageEnglish (US)
Pages (from-to)1804-1811
Number of pages8
JournalArthritis and Rheumatism
Volume52
Issue number6
DOIs
StatePublished - Jun 2005

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

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