Role of AP-1 complex in angiotensin II-mediated transforming growth factor-beta expression and growth of smooth muscle cells: using decoy approach against AP-1 binding site.
The cis element double-stranded oligodeoxynucleotides (ODN) ("decoy") approach has enabled us to clarify the responsible elements. Using this approach, we transfected AP-1 decoy ODN into VSMC cultured from WKY rats (WKY Adu) which produce latent TGF-beta, but not active TGF-beta, and Sprague-Dawley rats (CNC) which produce active and latent TGF-beta under Ang II-stimulation. AP-1, but not mismatched, decoy ODN abolished Ang II-stimulated TGF-beta gene expression and production in both Adu and CNC. However, AP-1 decoy did not alter DNA, RNA, and protein synthesis in Adu. In contrast, cell number was increased under Ang II stimulation by AP-1 decoy ODN in CNC without significant change in RNA and protein synthesis. These results showed that Ang II stimulated TGF-beta production through the AP-1 complex. In VSMC that produce active TGF-beta (CNC), the AP-1 complex stimulated by Ang II may inhibit cell growth through active TGF-beta production. Overall, this study demonstrates the utility of the decoy approach to study the specific function of cis elements in endogenous gene regulation such as Ang II-induced TGF-beta expression.
Morishita, R; Gibbons, GH; Horiuchi, M; Kaneda, Y; Ogihara, T; Dzau, VJ
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