Open AccessDiminished 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
Author(s) -
Prelog Martina,
Scheidegger Paul,
Peter Silvia,
Gershwin M. Eric,
Wick Georg,
Sgonc Roswitha
Publication year - 2005
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.21109
Subject(s) - procollagen peptidase , messenger rna , endocrinology , medicine , transforming growth factor , cell culture , microbiology and biotechnology , biology , genetics , gene
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 3 H‐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.