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https://hdl.handle.net/2440/61875
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Type: | Journal article |
Title: | Enhanced fibrillin-2 expression is a general feature of wound healing and sclerosis: potential alteration of cell attachment and storage of TGF-beta |
Author: | Brinckmann, J. Hunzelmann, N. Kahle, B. Rohwedel, J. Kramer, J. Gibson, M. Hubmacher, D. Reinhardt, D. |
Citation: | Laboratory Investigation, 2010; 90(5):739-752 |
Publisher: | Nature Publishing Group |
Issue Date: | 2010 |
ISSN: | 0023-6837 1530-0307 |
Statement of Responsibility: | Jürgen Brinckmann, Nico Hunzelmann, Birgit Kahle, Jürgen Rohwedel, Jan Kramer, Mark A Gibson, Dirk Hubmacher and Dieter P Reinhardt |
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. |
Keywords: | fibrillin sclerosis wound healing |
Rights: | Copyright 2010 USCAP |
DOI: | 10.1038/labinvest.2010.49 |
Published version: | http://dx.doi.org/10.1038/labinvest.2010.49 |
Appears in Collections: | Aurora harvest 5 Pathology publications |
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