The Role of Claudins in Homeostasis

Sequential expression of claudins, a family of tight junction proteins, along the nephron mirrors the sequential expression of ion channels and transporters. Only by the interplay of transcellular and paracellular transport can the kidney efficiently maintain electrolyte and water homeostasis in an organism. Although channel and transporter defects have long been known to perturb homeostasis, the contribution of individual tight junction proteins has been less clear. Over the past two decades, the regulation and dysregulation of claudins have been intensively studied in the gastrointestinal tract. Claudin expression patterns have, for instance, been found to be affected in infection and inflammation, or in cancer. In the kidney, a deeper understanding of the causes as well as the effects of claudin expression alterations is only just emerging. Little is known about hormonal control of the paracellular pathway along the nephron, effects of cytokines on renal claudin expression or relevance of changes in paracellular permeability to the outcome in any of the major kidney diseases. By summarizing current findings on the role of specific claudins in maintaining electrolyte and water homeostasis, this Review aims to stimulate investigations on claudins as prognostic markers or as druggable targets in kidney disease.