EGF and TGF-beta regulate neutral endopeptidase expression in renal vascular smooth muscle cells

• Published in: The American journal of physiology Vol. 272; no. 6 Pt 1; p. C1836
• Main Authors: Tharaux, P L, Stefanski, A, Ledoux, S, Soleilhac, J M, Ardaillou, R, Dussaule, J C
• Format: Journal Article
• Language: English
• Published: United States 01.06.1997
• Subjects: Animals; Cell Division - drug effects; Cell Membrane - enzymology; Cells, Cultured; Epidermal Growth Factor - pharmacology; Flow Cytometry; gamma-Aminobutyric Acid - analogs & derivatives; gamma-Aminobutyric Acid - metabolism; Gene Expression Regulation, Enzymologic - drug effects; Iodobenzenes - metabolism; Kidney Cortex - blood supply; Kinetics; Male; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - enzymology; Neprilysin - biosynthesis; Protease Inhibitors - metabolism; Rabbits; Time Factors; Transcription, Genetic - drug effects; Transforming Growth Factor beta - pharmacology
• ISSN: 0002-9513
• DOI: 10.1152/ajpcell.1997.272.6.c1836

We recently reported that neutral endopeptidase (NEP) expression on renal vascular smooth muscle cells (VSMC) was downregulated in the presence of serum. Here we examine the role of epidermal growth factor (EGF) and transforming growth factor-beta 1 (TGF-beta) in this downregulation and the consequences of the changes in NEP activity on their mitogenic effects. EGF inhibited NEP activity, whereas TGF-beta was stimulatory. Expression of the enzyme was studied by measuring the binding of [125I]RB-104, a specific NEP inhibitor, and the fluorescence intensity of NEP-labeled cells. Both parameters were decreased by EGF and were increased by TGF-beta. NEP mRNA expression in EGF-treated cells was reduced after 48 h. In contrast, it was increased in TGF-beta-treated cells. Interestingly, NEP inhibition influenced the mitogenic effect of EGF. Indeed, thiorphan, an NEP inhibitor, and an anti-NEP antibody decreased EGF-dependent [3H]thymidine incorporation and cell proliferation by approximately 50%. TGF-beta had no effect on VSMC growth. These results indicate that EGF but not TGF-beta participates in the downregulatory potency of serum on NEP expression in VSMC. They also demonstrate that the full effect of EGF on VSMC proliferation depends on intact NEP activity.