%0 Journal Article
%@ 1471-2199
%A Zhai, Yihui
%A Xu, Hong
%A Shen, Qian
%A Schaefer, Franz
%A Schmitt, Claus P.
%A Chen, Jing
%A Liu, Haimei
%A Liu, Jialu
%A Liu, Jiaojiao
%C London ; Berlin ; Heidelberg
%D 2018
%F heidok:24295
%I BioMed Central ; Springer
%J BMC molecular biology
%N 4
%P 1-9
%T pH-mediated upregulation of AQP1 gene expression through the Spi-B transcription factor
%U https://archiv.ub.uni-heidelberg.de/volltextserver/24295/
%V 19
%X 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.