| Summary: | 碩士 === 國防醫學院 === 生物及解剖學研究所 === 95 === Endothelin-1 (ET-1), synthesized and secreted by both vascular endothelial and vascular smooth muscle cells (VSMCs), plays an important role in the development of various circulatory disorders, including hypertension and atherosclerosis. According to our previous studies, ET-1 secreted from aortic smooth muscle cell of spontaneously hypertensive rats (SHR) was about 2.5 times higher than that of age-matched Wistar-Kyoto rats (WKY). We also demonstrated that GHF-1 binding sequence of the ET-1 promoter region was responsible for the enhancement of ET-1 expression. However, there was no GHF-1 expression in VSMCs of SHR. But we found Oct-1/2, which belonging to the same POU homeodomain family as GHF-1, could bind to the GHF-1 binding sequence with the co-factor C/EBPß. We also found that the expression of Oct-1 was similar in SHR and WKY but the expression of Oct-2 and C/EBPs were higher in SHR than in WKY. In order to clarify the transcription factor Oct-2 may responsible for the higher expression of ET-1 in VSMCs from SHR, an Oct-2 expressed construct was transfected to A10 and WKY VSMCs. Western blotting analysis was used to detect the expression of Oct-2 protein. Then, the effect of Oct-2 on the regulation of ET-1 promoter was detected by reporter assay. Our data showed the Oct-2 was expressed in both A10 and WKY VSMCs . We also found that Oct-2 could regulate ET-1 promoter activity in A10 and WKY VSMCs. These data demonstrate that Oct-2 is an important factor for ET-1 expression, and C/EBPβ may only play a co-factor role of the ET-1 promoter regulation in A10 and WKY VSMCs. Therefore, we infer that Oct-2 may be an important factor for ET-1 overexpression in SHR VSMCs.
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