Fibrillin-1 staining anomalies are associated with increased staining for TGF-beta and elastic fibre degradation; new clues to the pathogenesis of emphysema.

Autor: Koenders MM; Department of Biochemistry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands., Wismans RG, Starcher B, Hamel BC, Dekhuijzen RP, van Kuppevelt TH
Jazyk: angličtina
Zdroj: The Journal of pathology [J Pathol] 2009 Aug; Vol. 218 (4), pp. 446-57.
DOI: 10.1002/path.2548
Abstrakt: We recently demonstrated aberrant staining of fibrillin-1 in lung tissue specimens with emphysematous lesions. In this study, we have extended this observation by an elaborate analysis of the elastic fibre. Using domain-specific antibodies to fibrillin-1, and to other elastin fibre-associated molecules, lung tissue derived from patients without obvious clinical emphysema, but harbouring various degrees of microscopical emphysematous lesions, was analysed. In addition, the fibrillin-regulated growth factor TGF-beta was studied. Electron microscopy and biochemical analysis of desmosine (a marker for elastin) were also performed. Results were compared with lung tissue derived from patients with clinical emphysema. Domain-specific antibodies recognizing the C-terminal, N-terminal, and middle part of fibrillin-1 showed aberrant staining patterns associated with increasing degrees of microscopical emphysema. Staining for elastin, emilin-1, and fibulin-2 was, however, not aberrant. TGF-beta staining was markedly increased. On the electron microscopic, but not light microscopical, level, initial elastic fibre degradation was noticed in specimens with microscopical emphysema. Lung specimens from patients with clinical emphysema also displayed fragmented fibrillin-1 staining and, in addition, displayed extensive degradation of the elastic fibre. The results suggest that fibrillin-1 anomalies and TGF-beta overexpression are associated with initial events occurring during the emphysematous process. Based on these and other data, a mechanism for emphysematogenesis is proposed.
((c) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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