| Summary: | 碩士 === 國防醫學院 === 生物及解剖學研究所 === 94 === Endothelin-1(ET-1) is not only a potent vasoconstrictor but also a vascular smooth muscle cell (VSMC) growth factor. Endothelin type-A receptor(ET-AR) has a higher affinity for ET-1. Due to higher expression of ET-AR within VSMC and the vasoconstrictive potency of its ligand, ET-AR is believed to be involved in the pathophysiology of hypertension. From our previous study, the density of ET-1 binding sites was greater in spontaneously hypertensive rats (SHRs) than in Wistar-Kyoto (WKY) rats. In addition, we found that both total ET-AR protein and mRNA expression were greater in SHRs than in WKY rats. In order to understand the regulation of rat ET-AR gene expression, a profile of different length of rat ET-AR promoter region reporter vectors was constructed. Nucleotide sequences of the cloned DNA fragments were confirmed by restriction mapping and DNA sequencing. Promoter activities analysis were performed in A10 cells and cultured aortic smooth muscle cells from 4-week-old SHRs and WKY rats. These analyses demonstrated the existence of two negative regulatory elements (-2058 to -1599 and -1379 to -1143 bases) and one positive regulatory element (-1599 to -1379 bases ). ET-AR promoter at the region between -92 and -1 base, may responsible for the overexpression of ET-AR in SHR vascular smooth muscle cell.
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