Monitoring epithelial plasticity, one cell at a time

The kidneys maintain plasma volume and composition by adapting to shifts in the concentration of ions and other solutes. Some years ago, Schwartz and colleagues identified one such homeostatic mechanism, in which acidosis alters the cellular population within the cortical collecting duct (CCD) of the kidney. Over a period of days, acidosis induces one epithelial cell type in the CCD, the so called b-intercalated cells, to adopt the characteristics of another cell type, the a-intercalated cells. Intercalated cells of both types employ a proton ATPase and an anion antiporter system to transport H+ and HCO3? ions across the epithelium. However, because they differ in the distribution of these proteins on their apical and basolateral surfaces, these two cell types affect plasma pH in opposing directions: b cells secrete HCO3? toward the lumen, acidifying the plasma, whereas a cells reabsorb HCO3?, helping to neutralize plasma pH. Now, Schwartz et al. have revisited the b-to-a shift, this time using CCDs cultured ex vivo, a system that allowed them to observe the fates of individual cells over several hours following reduction of external pH. Just as is seen in the living kidney following a period of acidosis, CCD cells undergo a morphological change and shift their polarity to favor HCO3? reabsorption. Building on their earlier identification of the ECM protein hensin as a key factor in epithelial differentiation, the authors examined the effect of a hensin blocking antibody in their ex vivo system. They confirm that this antibody specifically inhibits the conversion to the a cell phenotype. Hensin is ubiquitously expressed, generally in a soluble form that has no effect on the intercalated cell polarity. Interestingly, however, the hensin binding protein galectin-3 is expressed by a but not b cells and appears to favor the formation of insoluble, ECM-bound hensin that is biologically active. With the ability to monitor individual cells in real time, it should be possible to tease apart the changes in mRNA and protein expression, cellular morphology, and adhesive interactions that drive this dramatic shift in cellular phenotyp

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