TGF-β promotes the formation of pyridinoline cross-links in fibrosis via the induction of LH2 expression

Autor: Anne-Marie Zuurmond, Annemarie J. van der Slot, Ruud A. Bank, David Abraham
Rok vydání: 2008
Předmět:
Zdroj: International Journal of Experimental Pathology. 85:A24-A25
ISSN: 0959-9673
DOI: 10.1111/j.0959-9673.2004.369ae.x
Popis: Introduction The hallmark of fibrosis is an excessive accumulation of collagen, a process in which TGF-β plays an important role. The deposited collagen shows an increase in pyridinoline cross-links, due to overhydroxylation of lysine residues within the telopeptides. As we have found that the enzyme responsible for the hydroxylation of the telepeptide lysine residues is lysyl hydroxylase-2 (LH2), it was examined whether LH2 is increased in fibrotic lesions. TGF-β is a key mediator in fibrosis, and therefore its effect on the formation of pyridinolines was examined. Material and methods Using real-time PCR, LH2 mRNA expression was measured in fibroblasts cultured from the fibrotic skin of systemic sclerosis (SSc) patients. Furthermore, the amount of pyridinoline cross-links was analysed in the matrix deposited by fibroblasts stimulated with TGF-β. Results Elevated LH2 mRNA expression levels were found in SSc fibroblasts, which result in increased amounts of pyridinoline cross-links. Furthermore, increased pyridinoline levels were found in collagen deposited by fibroblasts stimulated with TGF-β, which was a consequence of increased LH2 mRNA levels. Conclusion These data demonstrate for the first time that during fibrotic processes, TGF-β plays a key role in the formation of pyridinoline cross-links via the induction of LH2 expression.
Databáze: OpenAIRE
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