Influences of endogenous and exogenous TGF-beta on elastin in rat lung fibroblasts and aortic smooth muscle cells.

Abstract

The factors that regulate elastin production during neonatal lung development have not been elucidated. Previous investigations suggested that transforming growth factor-beta (TGF-beta) increases elastin production by neonatal rat lung fibroblasts (LF). We examined whether this effect of TGF-beta was unique to these cells or was evident in other neonatal cells, which constitutively produce elastin, or in cells from adults, whose constitutive elastin production is low. We have quantitated soluble elastin, elastin mRNA, and TGF-beta production in primary cultures of smooth muscle cells (SMC) and LF from neonatal and adult rats and have examined the alterations in soluble elastin and elastin mRNA that result from adding 100 pM exogenous TGF-beta 1 to these cultures. Unsupplemented cultures of LF and SMC obtained from neonatal rats exhibited higher steady-state levels of elastin mRNA and contained more soluble elastin in their culture medium than did cells from adult animals. When neonatal LF were supplemented with 100 pM TGF-beta 1, they showed a significant increase in the soluble elastin content of their culture medium and their steady-state elastin mRNA. Neither LF obtained from adults nor SMC obtained from neonatal or adult rats significantly increased their soluble elastin or steady-state elastin mRNA after the addition of exogenous TGF-beta. When neonatal LF were supplemented with an anti-TGF-beta neutralizing antibody, the soluble elastin content of the culture medium decreased significantly. These data suggest that the responsiveness of elastin expression to TGF-beta is limited to neonatal LF and that endogenous TGF-beta influences elastin production by neonatal LF.