Angiotensin II Stimulates Matrix Metalloproteinase Secretion in Human Vascular Smooth Muscle Cells via Nuclear Factor-κB and Activator Protein 1 in a Redox-Sensitive Manner

2005 ◽  
Vol 42 (5) ◽  
pp. 415-423 ◽  
Author(s):  
Michael Browatzki ◽  
Dina Larsen ◽  
Carolein A.H. Pfeiffer ◽  
Sven G. Gehrke ◽  
Joachim Schmidt ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Matrix Metalloproteinase ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Activator Protein 1

scholarly journals Angiotensin II Stimulates Transcription of Insulin-Like Growth Factor I Receptor in Vascular Smooth Muscle Cells: Role of Nuclear Factor-κB

Endocrinology ◽  
2006 ◽  
Vol 147 (3) ◽  
pp. 1256-1263 ◽  
Author(s):  
Yewei Ma ◽  
Liping Zhang ◽  
Tao Peng ◽  
Jizhong Cheng ◽  
Shilpa Taneja ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Promoter Activity ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Ang Ii ◽  
Mapk Kinase

Increased expression of the IGF-I receptor (IGF-IR) is associated with proliferation and survival of vascular smooth muscle cells (VSMCs). In cultured VSMCs, we reported that angiotensin II (Ang II) increases transcription and expression of IGF-IR. Now, we show that mesenteric arteries of rats infused with Ang II develop thickening and increased IGF-IR expression. To determine how Ang II transcriptionally regulates IGF-IR expression in VSMCs, we generated 5′-end deletions of the IGF-IR promoter and measured Ang II-induced promoter-luciferase activity in VSMCs. Activities from these promoter sequences suggested that the Ang II-responsive region is located between −270 and −135 of the IGF-IR promoter. Using a DNase I foot printing analysis, we identified two putative nuclear factor-κB (NF-κB)-like sequences located in the same region of the IGF-IR promoter. When we mutated either of these NF-κB-like sites, Ang II-induced IGF-IR promoter activity decreased sharply. Electrophoretic mobility gel shift, anti-p50 of NF-κB supershift and chromatin immunoprecipitation assays demonstrated that both the p65 and p50 subunits of NF-κB will bind to this Ang II response element in the IGF-IR promoter. When we blocked the Ras/MAPK kinase 1 pathway or the inhibitory-κB kinase pathway, both Ang II-induced IGF-IR promoter activity and expression of IGF-IR protein significantly declined. Our results indicate that the mechanism by which Ang II stimulates IGF-IR expression in VSMCs involves NF-κB binding to NF-κB sites in the IGF-IR promoter, leading to expression of IGF-IR through both Ras/MAPK kinase 1-and inhibitory-κB kinase-dependent pathways. Because IGF-IR is a major factor associated with thickening of mesenteric vessels, our results provide potential therapeutic targets.

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