| Summary: | 碩士 === 國防醫學院 === 生物化學研究所 === 99 === To date, thirteen mammalian aquaporins (AQPs) have been identified.AQP5 is selectively expressed in Salivary gland, lacrimal gland, sweat gland and lung alveolar epithelial cells. Xerostomia, the result of the decrease in secretion of saliva by salivary gland, is a complication of diabetes mellitus. It is not clear whether the reduced saliva production is due to decrease AQPs expression in salivary gland. However, the correlation between blood glucose concentration and AQP5 expression has not been reported. In this study, we used various cell lines as a model to investigate whether AQP5 gene expression is regulated by glucose concentration, and identify which transcription factors that may be involved in the regulation. Here, we demonstrated that AQP5 was induced by glucose which may cause the hypertonic stress. Either 5-Aza-CdR or TSA was able to modulate AQP5 gene expression in specific cell lines, such as H1299 and HaCaT cells, implies the functional role of epigenetic regulation. AQP5 gene was also up-regulated by the knockdown of DNMT3a or DNMT3b, suggesting that DNMT3a and DNMT3b are involved in the stable hyper-methylation of AQP5 gene. We further identified two transcription factors, Sp1 and C/EBPbeta enhanced the promoter activity of AQP5 gene in A253 cells. Taken together, our data suggest that the regulation of AQP5 gene expression is not only mediated through the epigenetic modification, primarily through the DNA hyper-methylation, but also mediated through the response to environmental change for the recruitment of specific transcription factors onto its promoter.
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