Diminished transforming growth factor beta2 production leads to increased expression of a profibrotic procollagen alpha2 type I messenger RNA variant in embryonic fibroblasts of UCD-200 chickens, a model for systemic sclerosis.

Autor: Prelog M; Innsbruck Medical University, Innsbruck, Austria., Scheidegger P, Peter S, Gershwin ME, Wick G, Sgonc R
Jazyk: angličtina
Zdroj: Arthritis and rheumatism [Arthritis Rheum] 2005 Jun; Vol. 52 (6), pp. 1804-11.
DOI: 10.1002/art.21109
Abstrakt: Objective: A procollagen alpha2(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 proalpha2(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 beta1 (TGFbeta1) and TGFbeta2 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 proalpha2(I) mRNA variant. TGFbeta1 stimulated the proliferation of UCD-200-CEF, but not NWL-CEF. The 115 bp:180 bp ratio was increased by TGFbeta1 in both NWL-CEF and UCD-CEF. TGFbeta2 and TGFbeta3 reduced the expression of the profibrotic proalpha2(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 TGFbeta2 than that produced by UCD-CEF. Inhibition of endogenous TGFbeta2 in NWL-CEF resulted in the same 115 bp:180 bp ratio as seen in untreated UCD-CEF.
Conclusion: TGFbeta2 reduces the expression of a profibrotic proalpha2(I) mRNA variant in UCD-200-CEF. The constitutive overproduction of this proalpha2(I) mRNA variant and the diminished synthesis of TGFbeta2 in untreated UCD-200-CEF suggest that TGFbeta2 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 TGFbeta2 in human systemic sclerosis.
Databáze: MEDLINE
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