PGE(1) SUPPRESSES THE INDUCTION OF COLLAGEN-SYNTHESIS BY TRANSFORMING GROWTH FACTOR-BETA(1) IN HUMAN CORPUS CAVERNOSUM SMOOTH-MUSCLE

Collagen synthesis has been examined in primary cultures of human corpus cavernosum smooth muscle cells (HCCSMC), the major mesenchymal cell type of the corpus cavernosum. These cultures were grown from human surgical specimens and characterized by morphological and biochemical characteristics. These cells express mRNA for transforming growth factor-beta(1) (TGF-beta(1)), a major regulator of extracellular matrix synthesis, as well as all three subtypes of TGF-beta receptors. Human corpus cavernosum smooth muscle cells primarily synthesize types I and III fibrillar collagen. Treatment of HCCSMC with exogenous TGF-beta(1) (80 pM.) induced a 2.5- to 4.5-fold increase in the synthesis of types I and III collagen and resulted in detectable levels of type V/XI collagen. Treatment of HCCSMC with the eicosanoid PGE(1) in combination with TGF-beta(1) suppressed the induction of collagen synthesis by TGF-beta(1) in a dose-dependent manner, with concomitant decreases in types I, III and V/XI: collagen. The expression of TGF-beta(1) mRNA as well as types I and II TGF-beta receptors was induced by exogenous TGF-beta(1). Transforming growth factor-beta(1) mRNA induction was suppressed by PGE(1). These data suggest that prostaglandins and TGF-beta(1) may play a key role in modulation of collagen synthesis in the corpus cavernosum, and in the regulation of fibrosis of the corpus cavernosum.