Development and Diseases of the Collecting Duct System

Abstract

The collecting duct of the mammalian kidney is important for the regulation of extracellular volume, osmolarity, and pH. There are two major structurally and functionally distinct cell types: principal cells and intercalated cells. The former regulates Na and water homeostasis, while the latter participates in acid-base homeostasis. In vivo lineage tracing using Cre recombinase or its derivatives such as CreGFP and CreER is a powerful new technique to identify stem/progenitor cells in their native environment and to decipher the origins of the tissue that they give rise to. Recent studies using this technique in mice have revealed multiple renal progenitor cell populations that differentiate into various nephron segments and collecting duct. In particular, emerging evidence suggests that like principal cells, most of intercalated cells originate from the progenitor cells expressing water channel Aquaporin 2. Mutations or malfunctions of the channels, pumps, and transporters expressed in the collecting duct system cause various human diseases. For example, gain-of-function mutations in ENaC cause Liddle's syndrome, while loss-of-function mutations in ENaC lead to Pseudohypoaldosteronism type 1. Mutations in either AE1 or V-ATPase B1 result in distal renal tubular acidosis. Patients with disrupted AQP2 or AVPR2 develop nephrogenic diabetes insipidus. A better understanding of the function and development of the collecting duct system may facilitate the discovery of new therapeutic strategies for treating kidney disease.

Aqp2+ Progenitor Cells Maintain and Repair Distal Renal Segments

“…ICs can be further classified into α -ICs and β -ICs. Mutations of the channels, pumps, and transporters in the DCT/CNT/CD are responsible for various human diseases 4 . Additionally, CNTs/CDs are also involved in the development of kidney fibrosis 5 – 9 …”

AQP2: Mutations Associated with Congenital Nephrogenic Diabetes Insipidus and Regulation by Post-Translational Modifications and Protein-Protein Interactions

“…Therefore, some infants may not be able to grow or gain weight at the normal rate. Adult patients gradually develop orthostatic hypotension, megacystis hydronephrosis, and hydroureter because of persistent polyuria (reviewed in [ 2 ]).…”

“…AVP stimulation of AVPR2 also activates the adenylyl cyclases AC3 and AC6, promoting conversion of ATP to cyclic adenosine monophosphate (cAMP) mobilizing cAMP-dependent kinases such as PKA to function in AQP2 trafficking. AQP2 translocation can also take place in a cAMP-independent manner (reviewed in [ 2 ]).…”

Genetic Renal Diseases: The Emerging Role of Zebrafish Models

“…As mentioned previously, some larval zebrafish models do not recapitulate the expected disease phenotype, which could be due to functional redundancy with duplicated paralogues, or other genes from the same family, or the lack of expression of the gene of interest at the larval stage. Also, zebrafish models are probably unsuitable to study genetic diseases affecting water homeostasis, such as hereditary nephrogenic diabetes insipidus, which is caused by either AVPR2 or AQP2 defects in humans [ 164 ]. A true orthologue of AQP2 (aquaporin 2) is lacking in the zebrafish [ 165 ].…”