Vasopressin-2 receptor signaling and autosomal dominant polycystic kidney disease: from bench to bedside and back again

Markus M Rinschen, Bernhard Schermer, Thomas Benzing
Journal of the American Society of Nephrology: JASN 2014, 25 (6): 1140-7
Blockade of the vasopressin-2 receptor (V2R) in the kidney has recently emerged as a promising therapeutic strategy in autosomal dominant polycystic kidney disease. The pathophysiologic basis of V2R-dependent cyst proliferation and disease progression, however, is not fully understood. Recent evidence suggests that polycystic kidney disease is characterized by defects in urinary concentrating mechanisms and subsequent deregulation of vasopressin excretion by the neurohypophysis. On the cellular level, several recent studies revealed unexpected crosstalk of signaling pathways downstream of V2R activation in the kidney epithelium. This review summarizes some of the unexpected roles of V2R signaling and suggests that vasopressin signaling itself may contribute crucially to loss of polarity and enhanced proliferation in cystic kidney epithelium.

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