AQP2-induced acceleration of renal cell proliferation involves the activation of a regulatory volume increase mechanism dependent on NHE2

DI GIUSTO G; CAPURRO C; RIVAROLA V; FORD P; CHRISTENSEN MJ

JOURNAL OF CELLULAR BIOCHEMISTRY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2016

0730-2312

We have previously shown in renal cells that expression of the water channelAquaporin 2 (AQP2) increases the rate of cell proliferation by shortening thetransit time through the S and G2/M phases of the cell cycle. This acceleration isdue, 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 Sphase. We hypothesize that in order to increase cell volume, RVD mechanismsmay be overtaken by regulatory volume increase mechanisms (RVI). In thisstudy, we investigated if the isoform 2 of the Na+/H+ exchanger (NHE2), themain ion transporter involved in RVI responses, contributed to the AQP2-increased renal cell proliferation. Three cortical collecting duct cell lines wereused: WT-RCCD1 (not expressing AQPs), AQP2-RCCD1 (transfected withAQP2) and mpkCCDc14 (with inducible AQP2 expression). We heredemonstrate, for the first time, that both NHE2 protein activity and expressionwas increased in AQP2-expressing cells. NHE2 inhibition decreased cellproliferation and delayed cell cycle progression by slowing S and G2/M phases