Transcriptional activation of matrix genes by transforming growth factor beta 1 in mesangial cells

The accumulation of mesangial matrix is a common histologic abnormality observed over the course of various glomerular diseases. To examine the role of transforming growth factor beta 1 (TGF-beta 1), a well-known regulator of extracellular matrix metabolism, in such processes, we studied the effects of this peptide on the gene expression of extracellular matrix components in cultured rat mesangial cells. TGF-beta 1 increased the mRNA levels for alpha 1 (I) and alpha 1 (IV) collagens and fibronectin. The increase in these mRNA levels was detectable 6 h after stimulation by TGF-beta 1. At 24 h, the mRNA levels for alpha 1 (I) and alpha 1 (IV) collagens and fibronectin increased 1.9-, 2.8- and 2.6-fold, respectively, above their basal levels. Concomitant treatment with cycloheximide did not prevent the stimulation by TGF-beta 1 and resulted in exceptional superinduction for the fibronectin gene. Concomitant treatment with actinomycin D completely inhibited the increase in the mRNA levels induced by TGF-beta 1. Furthermore, TGF-beta 1 showed no stabilizing effect on the transcripts. These results suggest that TGF-beta 1, which is released in glomerular injury, induces an increase in the transcription of the alpha 1 (I) and alpha 1 (IV) collagen and fibronectin genes in mesangial cells and may mediate the accumulation of the extracellular matrix in the mesangium.