Synergistic co-operation of signal transducer and activator of transcription 5B with activator protein 1 in angiotensin II-induced angiotensinogen gene activation in vascular smooth muscle cells

The binding sequences for signal transducer and activator of transcription (STAT) and activator protein 1 have been found in the promoter region of the angiotensinogen gene. We examined whether the elements for activator protein 1 and STAT5B function in angiotensinogen gene activation induced by angiotensin II in vascular smooth muscle cells. Stimulation with angiotensin II increased the level of angiotensinogen mRNA by 2.1-fold in vascular smooth muscle cells. The increased level of angiotensinogen mRNA occurred with concurrent elevations in the levels of STAT5B and c-Jun phosphorylation after stimulation with angiotensin II. Likewise, angiotensin II resulted in similar enhancements of the DNA-binding activity of STAT5B and c-Jun in angiotensin II-induced angiotensinogen expression. Notably, the STAT5B-DNA complex interacted with the c-Jun-DNA complex by forming a stable quaternary complex in angiotensin II-induced angiotensinogen expression. Our findings support a model in which co-operative interaction of STAT5B and activator protein 1 bound to the the promoter region provides maximal activation of angiotensinogen expression by angiotensin II in vascular smooth muscle cells.