Abstract
SUMMARY Growth factors are thought to be important in the pathogenesis of sarcoidosis and may mediate the differences between the phenotypes (self-limited disease vs. progressive lung disease). The aim of the study was to investigate the expression pattern of growth factors in sarcoidosis using gene expression array technology. We have performed a comprehensive genomic analysis, applying high density human GeneChip® probe arrays (U95A, Affymetrix) from blood from 12 patients with sarcoidosis (stage I: n=7, stage II/III: n=5) and 12 matched healthy controls. 260 growth-related genes were identified and analysed. Of these 260 growth genes, 193 (74 %) were expressed and 39 (15 %) differentially expressed in sarcoidosis. Of these significant genes, 19 were up- and 20 genes downregulated compared to controls. These growth factors can mainly be classified as growth factors related to inflammation, angiogenesis and fibroblast proliferation. Compared to the self-limited form of disease in patients with progressive lung involvement, growth factor genes associated with fibroblast proliferation seem to predominate (early growth response proteins 1, 2, alpha, growth arrest and DNA-damage-inducible protein, interleukin-6, interferon-related developmental regulator). In contrast, stage I disease is characterised by exaggerated gene expression of growth factors involved in angiogenesis (endothelin-1, heparin-binding EGF- like growth factor, endothelial cell growth factor 1, PDEGF, C-sisplatelet-derived growth factor 2, interferon-inducible peptide, VEGF, interleukin-1 genes, growth-arrest-specific protein). In conclusion, different growth factors are differentially expressed in sarcoidosis. Furthermore, the pattern of sarcoidosis-associated growth factor genes differs according to the sarcoidosis phenotype. Especially, the early growth response EGR-genes and genes related to the interferon-gamma pathway are predominatly upregulated in the progressive form of disease. 58
