Heparan sulphate proteoglycan in scleromyxedema promotes FGF-2 activity
| Autor: | Thomas F. Warner, David A. Wrone, Derek J. Cripps, Christoph Mundhenke, Andreas Friedl, Eliot C. Williams |
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| Rok vydání: | 2002 |
| Předmět: |
Adult
Male Lichenoid Eruptions Biology Fibroblast growth factor Pathology and Forensic Medicine Dermis Scleromyxedema Myxedema Extracellular medicine Humans Receptor Fibroblast Growth Factor Type 1 Receptor Ternary complex Skin Receptor Protein-Tyrosine Kinases Cell Biology Molecular biology Immunohistochemistry Receptors Fibroblast Growth Factor In vitro carbohydrates (lipids) medicine.anatomical_structure Alkaline phosphatase Fibroblast Growth Factor 2 Facial Dermatoses Heparan Sulfate Proteoglycans |
| Zdroj: | Pathology, research and practice. 198(10) |
| ISSN: | 0344-0338 |
| Popis: | Summary The cause of progressive dermal sclerosis, proliferation of fibroblasts, and collagen deposition in scleromyxedema is unknown. We analyzed the heparan sulphate proteoglycans (HSPG) in cutaneous nodules from a patient with scleromyxedema in order to ascertain their role in the binding of fibroblast growth factor (FGF) and promoting signaling complex assembly. Total heparan sulphate (HS) was detected with a mono-clonal antibody to HSPG on paraffin sections. Binding of FGF to HS was assessed using FGF-2 followed by anti-FGF-2 antibody. The formation of HS-mediated signaling complex was studied using soluble FR1-AP, which contains the extracellular domain of FGF receptor-1 linked to alkaline phosphatase (AP) and monoclonal anti-AP-antibody. Anti FGF-2 and anti-AP antibodies were visualized using the DAKO Envision Plus system. The dermal nodule of scleromyxedema contained ample HS and these bound FGF-2 and FR1-AP. Specificity was confirmed by prior incubation with heparitinase (no staining) and omission of FGF-2 (no staining). Increased amounts of HSPG were present in the dermal nodules of scleromyxedema compared to adjacent normal dermis and these bound FGF-2, immobilized the soluble receptor protein FGFR-1 and, therefore, formed a ternary complex composed of HSPG, FGF-2 and FGFR-1 in vitro. Since this complex resembles the signaling complex formed on live cells, HSPG in the nodules of scleromyxedema are in a configuration that promotes FGF activity. |
| Databáze: | OpenAIRE |
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