AQP2‐Induced Acceleration of Renal Cell Proliferation Involves the Activation of a Regulatory Volume Increase Mechanism Dependent on NHE2. Issue 5 (5th January 2017)

• Record Type: Journal Article
• Authors: Rivarola, Valeria; Di Giusto, Gisela; Christensen, María José; Ford, Paula; Capurro, Claudia
• Is Part Of: Journal of cellular biochemistry. Volume 118:Issue 5(2017)
• Page Start: 967
• Page End: 978
• Publication Date: 2017-01-05
• Subjects: AQUAPORIN 2 -- Na+/H+ EXCHANGER -- REGULATORY VOLUME INCREASE -- CELL PROLIFERATION; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.25602
• Languages: English
• ISSNs: 0730-2312

Abstract

ABSTRACT: We have previously shown in renal cells that expression of the water channel Aquaporin 2 (AQP2) increases the rate of cell proliferation by shortening the transit time through the S and G2 /M phases of the cell cycle. This acceleration is due, at least in part, to a down‐regulation of regulatory volume decrease (RVD) mechanisms when volume needs to be increased in order to proceed into the S phase. We hypothesize that in order to increase cell volume, RVD mechanisms may be overtaken by regulatory volume increase mechanisms (RVI). In this study, we investigated if the isoform 2 of the Na + /H + exchanger (NHE2), the main ion transporter involved in RVI responses, contributed to the AQP2‐increased renal cell proliferation. Three cortical collecting duct cell lines were used: WT‐RCCD1 (not expressing AQPs), AQP2‐RCCD1 (transfected with AQP2), and mpkCCDc14 (with inducible AQP2 expression). We here demonstrate, for the first time, that both NHE2 protein activity and expression were increased in AQP2‐expressing cells. NHE2 inhibition decreased cell proliferation and delayed cell cycle progression by slowing S and G2 /M phases only if AQP2 was expressed. Finally, we observed that only in AQP2‐expressing cells a NHE2‐dependent RVI response was activated in the S phase. These observations suggest that the AQP2‐increased proliferation involves the activation of a regulatory volume increase mechanism dependent on NHE2. Therefore, we propose that the accelerated proliferation of AQP2‐expressing cells requires a coordinated modulation of the RVD/RVI activity that contributes to cell volume changes during cell cycle progression. J. Cell. Biochem. 118: 967–978, 2017. © 2016 Wiley Periodicals, Inc. Abstract : We have previously shown in renal cells that expression of the water channel Aquaporin 2 (AQP2) increases the rate of cell proliferation. In this study, we investigated if the isoform 2 of the Na + /H + exchanger (NHE2), the main ion transporter involved in RVI responses, contributed to the AQP2‐increased renal cell proliferation. Our results showed that in AQP2‐expressing cells NHE2 expression and activity are higher leading to an activation of a NHE2‐mediated RVI response in the S phase of the cell cycle, which may be implicated in the increase the rate of cell proliferation.