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The expression of type XV collagen was studied in cultured human dermal fibroblasts exposed to transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta (IL-1beta), cytokines which have been shown previously to alter the expression of several extracellular matrix genes. TGF-beta enhanced the expression of the type XV collagen gene (COL15A1) in a time-dependent manner, up to 4.3-fold after 24 h of incubation, whereas TNF-alpha and IL-1beta reduced the mRNA steady-state levels by 32 and 80%, respectively. When TGF-beta and TNF-alpha were added together to the cultures, the stimulatory effect of TGF-beta on type XV collagen gene expression was abrogated, indicating antagonistic modulation by these 2 cytokines. These data suggest that the cytokines tested in this study may contribute to the regulation of type XV collagen synthesis in a variety of tissues which have recently been shown to express this particular collagen gene.

Type XV collagen is a recently identified member of the diverse family of collagens, its structure being characterized by extensive interruptions in the collagenous sequences. A combination of Northern blot hybridization of fetal and adult human tissues and in situ hybridization analyses of a fetus with Down's syndrome, several placentas, and adult skin were used to localize expression of its mRNAs. Northern blot analysis revealed marked expression in heart, skeletal muscle, and placenta tissues and moderate levels in the kidney and pancreas. Clear in situ hybridization signals were detected in fibroblasts and endothelial cells in all tissues studied. Examination of fetal heart, skeletal muscle, and smooth muscle tissues showed that the high type XV collagen mRNA level in the muscle RNA was localized not only to fibroblasts residing in the endomysium but also to myoblasts. Interestingly, type XV collagen mRNAs were also synthesized by certain epithelial cells in kidney, lung, pancreas, and placenta. It was the morphologically immature glomeruli in the kidney and the lower parts of the nephron, especially the collecting ducts, that contained these mRNAs but not the mature glomeruli or proximal tubules, suggesting differences in expression during development. These findings indicate a wide distribution of type XV collagen transcripts, the main producers being mesenchymally derived cells, particularly muscle cells and fibroblasts.