Kidney Res Clin Pract.  2019 Jun;38(2):145-158. 10.23876/j.krcp.19.002.

New insights into the transcriptional regulation of aquaporin-2 and the treatment of X-linked hereditary nephrogenic diabetes insipidus

Affiliations
  • 1Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
  • 2Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Korea. thkwon@knu.ac.kr

Abstract

The kidney collecting duct (CD) is a tubular segment of the kidney where the osmolality and final flow rate of urine are established, enabling urine concentration and body water homeostasis. Water reabsorption in the CD depends on the action of arginine vasopressin (AVP) and a transepithelial osmotic gradient between the luminal fluid and surrounding interstitium. AVP induces transcellular water reabsorption across CD principal cells through associated signaling pathways after binding to arginine vasopressin receptor 2 (AVPR2). This signaling cascade regulates the water channel protein aquaporin-2 (AQP2). AQP2 is exclusively localized in kidney connecting tubules and CDs. Specifically, AVP stimulates the intracellular translocation of AQP2-containing vesicles to the apical plasma membrane, increasing the osmotic water permeability of CD cells. Moreover, AVP induces transcription of the Aqp2 gene, increasing AQP2 protein abundance. This review provides new insights into the transcriptional regulation of the Aqp2 gene in the kidney CD with an overview of AVP and AQP2. It summarizes current therapeutic approaches for X-linked nephrogenic diabetes insipidus caused by AVPR2 gene mutations.

Keyword

Arginine vasopressin; Aquaporin-2; Gene expression regulation; G-protein coupled receptors; Nephrogenic diabetes insipidus

MeSH Terms

Aquaporin 2*
Arginine Vasopressin
Body Water
Cell Membrane
Diabetes Insipidus, Nephrogenic*
Gene Expression Regulation
Homeostasis
Kidney
Kidney Tubules, Collecting
Osmolar Concentration
Permeability
Phenobarbital
Receptors, Vasopressin
Water
Aquaporin 2
Arginine Vasopressin
Phenobarbital
Receptors, Vasopressin
Water
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