Transforming Growth Factor-β Regulation of Endothelin Expression in Rat Vascular Cell and Organ Cultures

Abstract

Transforming growth factor (TGF)-beta increases the production of the vasoactive peptide endothelin (ET) in cultures of vascular endothelial cells (EC) and vascular smooth muscle cells (VSMC), but the physiologic or pathologic significance of this regulation has not been determined. The present studies test the hypothesis that when EC and VSMC are in direct contact or close proximity, ET expression is, at least in part, dependent on TGF-beta. The effects of TGF-beta on ET-1 mRNA (Northern analysis and reverse transcription polymerase chain reaction) and peptide (radioimmunoassay) levels were assessed in rat EC and VSMC and vascular organ cultures. TGF-beta2 (1 ng/ml) increased ET-1 mRNA in VSMC and EC plus VSMC cultures and increased ET-1 peptide in EC, VSMC, and EC plus VSMC cultures. TGF-beta2 also increased ET-1 mRNA and peptide in vascular organ cultures. Antibodies that neutralized the activities of TGF-beta1 and TGF-beta2 decreased ET-1 mRNA in EC plus VSMC cultures and in vascular organ cultures. These data indicate that when EC and VSMC are in direct contact or close proximity, TGF-beta increases ET expression and active TGF-beta is present and promotes ET expression. These data suggest that TGF-beta is a determinant of vascular ET expression in vivo, and that TGF-beta regulation of ET expression would affect cardiovascular function in health and disease.