Abstract
Wound healing and sclerosis are characterized by an increase of extracellular matrix proteins, which are characteristically expressed in the embryo-fetal period. We analyzed the expression of fibrillin-2, which is typically found in embryonic tissues, but only scarcely in adult skin. In wound healing and sclerotic skin diseases such as lipodermatosclerosis and scleroderma, a marked increase of fibrillin-2 expression was found by immunohistology. Double labelling of fibrillin-2 and tenascin-C, which is also expressed in wound healing and sclerosis, showed co-localization of both proteins. Solid-phase and slot blot-overlay assays showed a dose-dependent binding of the recombinant N-terminal half of fibrillin-2 (rFBN2-N) to tenascin-C. Real-time PCR showed an increase of the fibrillin-2 gene expression in cell culture triggered by typical mediators for fibroblast activation such as serum, IL-4, and TGF-Β. By contrast, prolonged hypoxia is not associated with changes in fibrillin-2 expression. Tenascin-C is an anti-adhesive substrate for fibroblasts, whereas fibrillin-2 stimulates cell attachment. Attachment assays using mixed substrates showed decreased cell attachment when tenascin-C and rFBN2-N were coated together, compared with the attachment to rFBN2-N alone. Fibrillins are involved in storage and activation of TGF-Β. Immunohistology with an antibody against the latency-associated peptide (LAP (TGF-Β1)) showed a marked increase of inactive LAP-bound TGF-Β1 in wound healing and sclerotic skin whereas normal skin showed only a weak expression. Double immunofluorescence confirmed a partial colocalization of both proteins. In conclusion, we show that a stimulation of the fibrillin-2 expression is a characteristic feature of fibroblasts present in wound healing and sclerosis, which may be involved in the alteration of cell attachment and storage of inactive TGF-Β in the matrix.
| Original language | English |
|---|---|
| Journal | Laboratory Investigation |
| Volume | 90 |
| Issue number | 5 |
| Pages (from-to) | 739-752 |
| Number of pages | 14 |
| ISSN | 0023-6837 |
| DOIs | |
| Publication status | Published - 01.05.2010 |
Funding
We thank Dr Ruth Chiquet-Ehrismann, Friedrich Miescher Institute of Biomedical Research, Basel, Switzerland for supporting the study. We also thank Julia Fischer, Martina Alexander, Christine Fagotto-Kaufmann and Heiko Steenbock for excellent technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft (Grants Br1146/3–1 and 3–3), the Deutsche Gesellschaft für Phlebologie, the Bundesministerium für Bildung und Forschung (German Network for Systemic Scleroderma), and the Canadian Institutes of Health Research (MOP-68836).
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
