LOCALIZATION OF ELASTIN MESSENGER-RNA AND TGF-BETA-1 IN RAT AORTA ANDCAUDAL ARTERY AS A FUNCTION OF AGE

Several in vitro studies have previously demonstrated that the additio n of TGF-beta to aortic smooth muscle cells or skin fibroblasts stimul ates elastin synthesis. It is not clear however whether, in vivo, TGF- beta participates in the regulation of elastin synthesis, especially i n physiological conditions. The aim of our study was to explore the lo calization of elastin mRNA and TGF-beta 1 in the rat thoracic aorta (a n elastic artery) and caudal artery (a muscular artery). Elastin mRNA was localized by in situ hybridization and quantified using Northern b lot analysis. TGF-beta 1 was detected using immunohistochemistry. The study was carried out as a function of age (rats of 3, 10, 20, and 30 months). We observed that TGF-beta 1 immunoreactivity is present predo minantly, but not exclusively, at the sites of elastin synthesis as de termined by elastin mRNA detection: in smooth muscle cells in the aort a and in endothelial cells in the caudal artery. The ability of exogen ously added TGF-beta 1 (0.001-10 ng/ml) to modulate the steady-state l evels of elastin mRNA in primary cultures of endothelial cells, smooth muscle cells, and fibroblasts isolated from the thoracic aorta was al so studied. At the highest concentration used, elastin mRNA levels inc reased 5-fold in endothelial cells and 11-fold in smooth muscle cells. The demonstration that TGF-beta 1 immunoreactivity is present at the sites of elastin synthesis in the thoracic aorta and in the caudal art ery and the observation that TGF-beta 1 induces an increase in elastin mRNA levels in cultured endothelial cells and smooth muscle cells sug gest that TGF-beta 1 may be implicated, at least in part, in the physi ological regulation of elastin gene expression.