In: BMC molecular biology, 19 (2018), Nr. 4. S. 1-9. ISSN 1471-2199

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PDF, Englisch Download (1MB) | Lizenz: pH-mediated upregulation of AQP1 gene expression through the Spi-B transcription factor von Zhai, Yihui ; Xu, Hong ; Shen, Qian ; Schaefer, Franz ; Schmitt, Claus P. ; Chen, Jing ; Liu, Haimei ; Liu, Jialu ; Liu, Jiaojiao steht unter einer Creative Commons Namensnennung 4.0

Abstract

Background: Bicarbonate-based peritoneal dialysis (PD) fluids enhance the migratory capacity and damage-repair ability of human peritoneal mesothelial cells by upregulating AQP1. However, little is known about the underlying molecular mechanisms.

Results: Here we used HEK-293T cells to investigate the effect of pH on AQP1 gene transcription levels. We found that AQP1 mRNA levels increases with pH. Transfection of HEK-293T cells with luciferase reporter vectors containing different regions of the AQP1 promoter identified an upstream region in the AQP1 gene between − 2200 and – 2300 bp as an enhancer required for pH-mediated regulation of AQP1 expression. Site-directed mutagenesis of this specific promoter region revealed a critical region between − 2257 and − 2251 bp, and gene knock-down experiments and ChIP assays suggested that the Spi-B transcription factor SPIB is involved in pH-mediated regulation of AQP1 expression.

Conclusions: We identified an upstream region in the AQP1 gene and the transcription factor SPIB that are critically involved in pH-mediated regulation of AQP1 expression. These findings provide the basis for further studies on the pH- and buffer-dependent effects of PD fluids on peritoneal membrane integrity and function.