Na+/H+ exchanger isoform 1 activity in AQP2-expressing cells can be either proliferative or anti-proliferative depending on extracellular pH

MARINA MAZZOCCHI; GISELA DI GIUSTO; MICAELA PORTA; ALEJANDRO PIZZONI; NATALIA BELTRAMONE; PAULA FORD; CLAUDIA CAPURRO; VALERIA RIVAROLA

JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY

SERVICIO PUBLICACIONES UNIVERSIDAD NAVARRA

Año: 2020 vol. 76 p. 37 - 48

1138-7548

We have previously shown in renal cells that expression of the water channel Aquaporin-2 increases cell proliferation by a regulatory volume mechanism involving Na+/H+ exchanger isoform 2. Here, we investigated if Aquaporin-2 (AQP2) also modulates Na+/H+ exchanger isoform 1-dependent cell proliferation. We use two AQP2-expressing cortical collecting duct models: one constitutive (WT or AQP2- transfected RCCD1 cell line) and one inducible (control or vasopressin-induced mpkCCDc14 cell line). We found that Aquaporin-2 modifies Na+/H+ exchanger isoform 1 contribution to cell proliferation. In Aquaporin-2-expressing cells, Na+/H+ exchanger isoform 1 becomes anti-proliferative. In acid media, Na+/H+ exchanger isoform 1 contribution turned from anti-proliferative to proliferative only in AQP2-expressing cells. We also found that, in AQP2-expressing cells, F-actin augmented when Na+/H+ exchanger isoform 1-dependent proliferation raised. Moreover, we found that all Na+/H+ exchanger-dependent effects on proliferation linked to Aquaporin-2 relied on Transient Receptor Potential Subfamily V calcium channels activity. In conclusion, our data show that, in collecting duct cells, the water channel AQP2 modulates NHE1-dependent cell proliferation. In AQP2-expressing cells, at physiological pH, NHE1 function is anti-proliferative and, at acidic pH, NHE1 function is proliferative.