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This document is an editorial published in Frontiers in Physiology titled "Renal physiology: epithelial cell mechanics." The editorial emphasizes the importance of understanding the mechanical properties of renal epithelial cells in both health and disease. It highlights key themes in epithelial cell mechanics, including energy balance, fluid and electrolyte transport, and primary cilium function. The editorial also discusses the role of renal epithelial cell mechanics in kidney disorders such as obesity-related kidney diseases, acute kidney injury, and diabetic kidney disease. The document concludes by acknowledging the contributions of the authors and reviewers to the research topic. [Extracted from the article]

A high renal oxygen (O2) need is primarily associated with the renal tubular O2 consumption (VO2) necessary for a high rate of sodium (Na+) transport. Limited O2 availability leads to increased levels of adenosine, which regulates the kidney via activation of both A1 and A2A adenosine receptors (A1R and A2AR, respectively). The relative contributions of A1R and A2AR to the regulation of renal Na+ transport and VO2 have not been determined. We demonstrated that A1R activation has a dose‐dependent biphasic effect on both renal Na+/H+ exchanger‐3 (NHE3), a major player in Na+ transport, and VO2. Here, we report concentration‐dependent effects of adenosine: less than 5 × 10−7 M adenosine‐stimulated NHE3 activity; between 5 × 10−7 M and 10−5 M adenosine‐inhibited NHE3 activity; and greater than 10−5 M adenosine reversed the change in NHE3 activity (returned to baseline). A1R activation mediated the activation and inhibition of NHE3 activity, whereas 10−4 M adenosine had no effect on the NHE3 activity due to A2AR activation. The following occurred when A1R and A2AR were activated: (a) Blockade of the A2AR receptor restored the NHE3 inhibition mediated by A1R activation, (b) the NHE‐dependent effect on VO2 mediated by A1R activation became NHE independent, and (c) A2AR bound to A1R. In summary, A1R affects VO2 via NHE‐dependent mechanisms, whereas A2AR acts via NHE‐independent mechanisms. When both A1R and A2AR are activated, the A2AR effect on NHE3 and VO2 predominates, possibly via an A1R–A2AR protein interaction. A2AR–A1R heterodimerization is proposed as the molecular mechanism enabling the NHE‐independent control of renal VO2. [ABSTRACT FROM AUTHOR]

The high requirement of O2 in the renal proximal tubule stems from a high rate of Na+ transport. Adenosine A1 receptor (A1R) activation regulates Na+ transport in this nephron segment. Thus, the effect of the acute activation and the mechanisms of A1R on the rate of O2 consumption were evaluated. The A1R-antagonist, 8-cyclopentyl-1,3-dipropylxanthine (CPX) and adenosine deaminase (ADA), which metabolize endogenous adenosine, reduced O2 consumption (40-50%). Replacing Na+ in the buffer reversed the ADA- or CPX-mediated reduction of O2 consumption. Blocking the Na/H-exchanger activity, which decreases O2 usage per se, did not enhance the ADA- or CPX-induced inhibition of O2 consumption. These data indicate that endogenous adenosine increases O2 usage via the activation of Na+ transport. In the presence of endogenous adenosine, A1R was further activated by the A1R-agonist N6-cyclopentyladenosine (CPA); CPA inhibited O2 usage (30%) and this effect also depended on Na+ transport. Moreover, a low concentration of CPA activated O2 usage in tissue pretreated with ADA, whereas a high concentration of CPA inhibited O2 usage; both effects depended on Na+. Protein kinase C signaling mediated the inhibitory effect of A1R, while adenylyl cyclase mediated its stimulatory effect on O2 consumption. In summary, increasing the local concentrations of adenosine can either activate or inhibit O2 consumption via A1R, and this mechanism depends on Na+ transport. The inhibition of O2 usage by A1R activation might restore the compromised balance between energy supply and demand under pathophysiological conditions, such as renal ischemia, which results in high adenosine production. J. Cell. Physiol. 230: 3093-3104, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Na+/H+ exchanger-3 (NHE3) plays an essential role in maintaining sodium and fluid homeostasis in the intestine and kidney epithelium. Thus, NHE3 is highly regulated and its function depends on binding to multiple regulatory proteins. Ezrin complexed with NHE3 affects its activity via not well-defined mechanisms. This study investigates mechanisms by which ezrin regulates NHE3 activity in epithelial Opossum Kidney cells. Ezrin is activated sequentially by phosphatidylinositol-4,5-bisphosphate (PIP2) binding and phosphorylation of threonine 567. Expression of ezrin lacking PIP2 binding sites inhibited NHE3 activity (-40%) indicating that ezrin binding to PIP2 is required for preserving NHE3 activity. Expression of a phosphomimetic ezrin mutated at the PIP2 binding region was sufficient not only to reverse NHE3 activity to control levels but also to increase its activity (+80%) similar to that of the expression of ezrin carrying the phosphomimetic mutation alone. Calcineurin Homologous Protein-1 (CHP1) is part, with ezrin, of the NHE3 regulatory complex. CHP1-mediated activation of NHE3 activity was blocked by expression of an ezrin variant that could not be phosphorylated but not by an ezrin variant unable to bind PIP2. Thus, for NHE3 activity under baseline conditions not only ezrin phosphorylation, but also ezrin spatial-temporal targeting on the plasma membrane via PIP2 binding is required; however, phosphorylation of ezrin appears to overcome the control of NHE3 transport. CHP1 action on NHE3 activity is not contingent on ezrin binding to PIP2 but rather on ezrin phosphorylation. These findings are important in understanding the interrelation and dynamics of a CHP1-ezrin-NHE3 regulatory complex. [ABSTRACT FROM AUTHOR]