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The possible role of prostaglandin E2 (PGE2) on the formation of collagens and fibronectin in cultured rat mesangial cells (MC) was studied. The effect of exogenous PGE2 was analyzed by the measurement of steady-state mRNA levels of the extracellular matrix components and by the secretion of these matrix components into cell culture supernatants. PGE2, in a dose-dependent manner, reduced mRNA levels of alpha 1(I) and alpha 1(III) procollagens but had little effect on alpha 1(IV) procollagen and fibronectin mRNA. In addition to its role on mRNA levels, PGE2 reduced the secretion of all studied collagen types into the cell culture supernatants. To evaluate a possible role of intracellular cAMP in the mediation of the PGE2 effects, MC were incubated with the cAMP analogue 8-bromo-cAMP (8brcAMP). In contrast to PGE2, 8brcAMP (1 mM) had no effect on mRNA expression of procollagen Types I and III over the studied time period (1 to 48 h). Furthermore, 8brcAMP stimulated collagen secretion into the cell supernatant after 48 h of incubation. These data demonstrate that PGE2 reduces mRNA levels of procollagen Types I and III in cultured MC, although the biosynthesis of all studied extracellular matrix components is inhibited. These alterations seem to be independent of intracellular cAMP, because the cAMP analogue 8brcAMP does not mimic the PGE2 effects on steady-state mRNA expression and collagen secretion of the studied extracellular matrix components.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of prostaglandin E2 on mRNA expression and secretion of collagens I, III, and IV and fibronectin in cultured rat mesangial cells.