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(Circulation Research. 1995;77:1070-1076.)
© 1995 American Heart Association, Inc.

Articles

Multiple Growth Factors Modulate mRNA Expression of Angiotensin II Type-2 Receptor in R3T3 Cells

Toshihiro Ichiki, Yoshikazu Kambayashi, Tadashi Inagami

From the Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tenn.

Correspondence to Tadashi Inagami, PhD, Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232.

Abstract Previous studies showed that angiotensin II type-2 receptor (AT₂) sites were increased when R3T3 cells were growth arrested and decreased when they were stimulated with fibroblast growth factor or serum. We examined the effects of several other growth factors on the expression of AT₂ mRNA to clarify the relation between the AT₂ receptor and growth factors. R3T3 cells were cultured in the medium containing 10% FCS until they were confluent, and then serum was removed. AT₂ mRNA was increased after serum was depleted, and the expression level reached a plateau after 2 days of serum depletion. The presence of serum (10%), fibroblast growth factor (10 ng/mL), or lysophosphatidic acid (1 µmol/L) reduced the AT₂ mRNA expression. Phorbol ester (1 to 100 nmol/L) also suppressed the AT₂ mRNA expression in a dose-dependent manner. Interleukin-1ß (1 ng/mL) enhanced the AT₂ mRNA expression 1.6-fold and the AT₂ receptor number 1.4-fold. Insulin (100 nmol/L) enhanced AT₂ mRNA expression 1.4-fold and the AT₂ receptor number 1.6-fold. These results suggest that AT₂ mRNA expression is modulated by multiple growth factors in both positive and negative directions. The presence of potential cis DNA elements that respond to interleukin-1ß (CCAAT enhancer binding protein site), insulin [insulin response sequence of phospho(enol)pyruvate carboxykinase gene], and phorbol ester (AP-1 site) in the promoter region of the mouse AT₂ gene suggests that the effects of these growth factors and phorbol ester may be mediated via these cis DNA elements.

Key Words: AT₂ receptors • mRNA expression • R3T3 cells • growth factor

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