Aquaporin 2-increased renal cell proliferation is associated with cell volume regulation.
We have previously demonstrated that in renal cortical collecting duct cells (RCCD(1)) the expression of the water channel Aquaporin 2 (AQP2) raises the rate of cell proliferation. In this study, we investigated the mechanisms involved in this process, focusing on the putative link between AQP2 expression, cell volume changes, and regulatory volume decrease activity (RVD). Two renal cell lines were used: WT-RCCD(1) (not expressing aquaporins) and AQP2-RCCD(1) (transfected with AQP2). Our results showed that when most RCCD(1) cells are in the G(1)-phase (unsynchronized), the blockage of barium-sensitive K(+) channels implicated in rapid RVD inhibits cell proliferation only in AQP2-RCCD(1) cells. Though cells in the S-phase (synchronized) had a remarkable increase in size, this enhancement was higher and was accompanied by a significant down-regulation in the rapid RVD response only in AQP2-RCCD(1) cells. This decrease in the RVD activity did not correlate with changes in AQP2 function or expression, demonstrating that AQP2-besides increasing water permeability-would play some other role. These observations together with evidence implying a cell-sizing mechanism that shortens the cell cycle of large cells, let us to propose that during nutrient uptake, in early G(1), volume tends to increase but it may be efficiently regulated by an AQP2-dependent mechanism, inducing the rapid activation of RVD channels. This mechanism would be down-regulated when volume needs to be increased in order to proceed into the S-phase. Therefore, during cell cycle, a coordinated modulation of the RVD activity may contribute to accelerate proliferation of cells expressing AQP2.
Laboratorio de Biomembranas, Facultad de Medicina, Departamento de Fisiología y Biofísica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Gisela
G
Di Giusto
Pilar
P
Flamenco
Valeria
V
Rivarola
Juan
J
Fernández
Luciana
L
Melamud
Paula
P
Ford
Claudia
C
Capurro
D000818:Animals; D051399:Aquaporin 2 / Q000235:genetics / Q000378:metabolism*; D017609:Barium Compounds / Q000494:pharmacology; D020013:Calcium Signaling; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability; D049109:Cell Proliferation / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects*; D002712:Chlorides / Q000494:pharmacology; D005434:Flow Cytometry; D059585:G1 Phase Cell Cycle Checkpoints; D007668:Kidney / Q000166:cytology*; D018715:Microscopy, Video; D009997:Osmotic Pressure; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D012430:Ruthenium Red / Q000494:pharmacology; D016196:S Phase; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism; D014162:Transfection
C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D017609:Barium Compounds; D002712:Chlorides; D015221:Potassium Channels; D050916:TRPV Cation Channels; C486577:Trpv4 protein, rat; C024986:barium chloride; D012430:Ruthenium Red