Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transgenic mouse models of aquaporin (AQP) deletion and mutation have been instructive in elucidating the role of AQPs in renal physiology. Mice lacking AQP1 are unable to concentrate their urine because of low water permeability in the proximal tubule, thin descending limb of Henle, and outer medullary descending vasa recta, resulting in defective near-isosmolar fluid absorption in the proximal tubule and defective countercurrent multiplication. Mice lacking functional AQP2, AQP3, or AQP4 manifest various degrees of nephrogenic diabetes insipidus resulting from reduced collecting duct water permeability. Mice lacking AQP7 and AQP8 can concentrate their urine fully, although AQP7 null mice manifest an interesting defect in glycerol reabsorption. Two unexpected renal phenotypes of AQP null mice have been discovered recently, including defective proximal tubule cell migration in AQP1 deficiency, and cystic renal disease in AQP11 deficiency. AQPs thus are important in several aspects of the urinary concentrating mechanism and in functions unrelated to tubular fluid transport. The mouse phenotype data suggest the renal AQPs as targets for the development of aquaretics and potentially for therapy of cystic renal disease and acute renal injury.
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PMID:Roles of aquaporins in kidney revealed by transgenic mice. 1671 93

Transgenic mice lacking renal aquaporins (AQPs), or containing mutated AQPs, have been useful in confirming anticipated AQP functions in renal physiology and in discovering new functions. Mice lacking AQPs 1-4 manifest defects in urinary concentrating ability to different extents. Mechanistic studies have confirmed the involvement of AQP1 in near-isosmolar fluid absorption in the proximal tubule, and in countercurrent multiplication and exchange mechanisms that produce medullary hypertonicity in the antidiuretic kidney. Deletion of AQPs 2-4 impairs urinary concentrating ability by reduction of transcellular water permeability in the collecting duct. Recently created transgenic mouse models of nephrogenic diabetes insipidus produced by AQP2 gene mutation offer exciting possibilities to test new drug therapies. Several unanticipated AQP functions in kidney have been discovered recently that are unrelated to their role in transcellular water transport. There is evidence for involvement of AQP1 in kidney cell migration after renal injury, of AQP7 in renal glycerol clearance, of AQP11 in prevention of renal cystic disease, and possibly of AQP3 in regulation of collecting duct cell proliferation. Future work in renal AQPs will focus on mechanisms responsible for these non-fluid-transporting functions, and on the development of small-molecule AQP inhibitors for use as aquaretic-type diuretics.
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PMID:Dissecting the roles of aquaporins in renal pathophysiology using transgenic mice. 1851 83

The kidney is a model organ for transport physiology (Nielsen 1996). AQPs are well-characterized in mammalian kidneys, where they facilitate transepithelial water reabsorption. Most renal AQPs are expressed either in proximal tubule cells or in collecting duct principal cells, which are known as sites for water reabsorption. AQP1 is present in both apical and basolateral membranes of proximal tubules, and in descending limbs of Henle's loop where 70% of filtrated water is isoosmotically reabsorbed (King and Agre 1996). AQP2 is expressed in principal cells of the collecting duct; in response to vasopressin, AQP2 translocates from intracellular vesicles to the apical plasma membranes, thereby increasing water permeability to concentrate urine (Nielsen et al. 1993, 1995; Knepper 1997; Schrier 2006). AQP3 and AQP4 reside in the basolateral membranes of collecting duct principal cells, where they may provide the exit pathways for urine. AQP7, AQP8, and AQP11 are also present in the proximal tubules (Nielsen et al. 1998).A rat cDNA clone encoding AQP6 was isolated by PCR-based homologous cloning from a rat kidney cDNA library (Ma et al. 1993; Yasui et al. 1999). AQP6 has high sequence homology to AQP0, AQP2, and AQP5. A human AQP6 was also cloned (Ma et al. 1996). Interestingly, the genes encoding AQP2, AQP5, and AQP6 are mapped to chromosome band 12q13 as a family gene cluster at this locus (Ma et al. 1997). Nevertheless, AQP6 is distinct from AQP0, AQP2, and AQP5 in terms of function. Among the renal aquaporins mentioned above, AQP6 has a unique distribution and a distinct function.
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PMID:pH regulated anion permeability of aquaporin-6. 1909 84

Aquaporins (AQPs) are key players regulating urinary-concentrating ability. To date, eight aquaporins have been characterized and localized along the nephron, namely, AQP1 located in the proximal tubule, thin descending limb of Henle, and vasa recta; AQP2, AQP3 and AQP4 in collecting duct principal cells; AQP5 in intercalated cell type B; AQP6 in intercalated cells type A in the papilla; AQP7, AQP8 and AQP11 in the proximal tubule. AQP2, whose expression and cellular distribution is dependent on vasopressin stimulation, is involved in hereditary and acquired diseases affecting urine-concentrating mechanisms. Due to the lack of selective aquaporin inhibitors, the patho-physiological role of renal aquaporins has not yet been completely clarified, and despite extensive studies, several questions remain unanswered. Until the recent and large-scale development of genetic manipulation technology, which has led to the generation of transgenic mice models, our knowledge on renal aquaporin regulation was mainly based on in vitro studies with suitable renal cell models. Transgenic and knockout technology approaches are providing pivotal information on the role of aquaporins in health and disease. The main goal of this review is to update and summarize what we can learn from cell and animal models that will shed more light on our understanding of aquaporin-dependent renal water regulation.
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PMID:Cell culture models and animal models for studying the patho-physiological role of renal aquaporins. 2218 94

The membrane water channel aquaporin (AQP) family is composed of 13 isoforms in mammals, eight of which are reportedly expressed in the kidney: AQP1, 2, 3, 4, 6, 7, 8, and 11. These isoforms are differentially expressed along the renal tubules and collecting ducts. AQP1 and 7 are distributed in the proximal tubules, whereas AQP2, 3, and 4 occur in the collecting duct system. They play important roles in the reabsorption of water and some solutes across the plasma membrane. In contrast to other aquaporins found in the kidney, AQP6, 8, and 11 are localized to the cytoplasm rather than to the apical or basolateral membranes. It is therefore doubtful that these isoforms are directly involved in water or solute reabsorption. AQP6 is localized in acid-secreting type A intercalated cells of the collecting duct. AQP8 has been found in the proximal tubule but its cellular location has not yet been defined by immunohistochemistry. AQP11 seems to be localized in the endoplasmic reticulum (ER) of proximal tubule cells. Interestingly, polycystic kidneys develop in AQP11-null mice. Many vacuole-like structures are seen in proximal tubule cells in kidneys of newborn AQP11-null mice. Subsequently, cysts are generated, and most of the mice die within a month due to severe renal failure. Although ER stress and impairment of polycystin-1, the product of the gene mutated in autosomal-dominant polycystic kidney disease, are possible causes of cystogenesis in AQP11-null mice, the exact mechanism of pathogenesis and the physiological function of AQP11 are yet to be resolved.
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PMID:The distribution and function of aquaporins in the kidney: resolved and unresolved questions. 2679 62

Several aquaporin (AQP )-type water channels are expressed in kidney: AQP1 in the proximal tubule, thin descending limb of Henle, and vasa recta; AQP2 -6 in the collecting duct; AQP7 in the proximal tubule; AQP8 in the proximal tubule and collecting duct; and AQP11 in the endoplasmic reticulum of proximal tubule cells. AQP2 is the vasopressin-regulated water channel that is important in hereditary and acquired diseases affecting urine-concentrating ability. The roles of AQPs in renal physiology and transepithelial water transport have been determined using AQP knockout mouse models. This chapter describes renal physiologic insights revealed by phenotypic analysis of AQP knockout mice and the prospects for further basic and clinical studies.
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PMID:Aquaporins in Urinary System. 2825 71

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by the mutation of polycystins (PC-1 or PC-2), in which cysts start from the collecting duct to extend to all nephron segments with eventual end stage renal failure. The cyst development is attenuated by a vasopressin V2 receptor antagonist tolvaptan which, however, will not affect proximal tubule cysts devoid of V2 receptor. Aquaporin-11 (AQP11) is expressed selectively in the proximal tubule of the kidney and AQP11-null kidneys have a disruptive PC-1 trafficking to the plasma membrane to develop polycystic kidneys. Here, we analyzed AQP11-null kidneys at the beginning of cyst formation by quantitative proteomic analysis using Tandem Mass Tag (TMT). Among ~ 1200 identified proteins, 124 proteins were differently expressed by > 1.5 or < 0.8 fold change. A pancreatic stone inhibitor or a growth factor, lithostathine-1 (Reg1) was most enhanced by 5 folds which was confirmed by western blot, while mitochondria-related proteins were downregulated. The identified proteins will be new target molecules for the treatment of proximal tubular cysts and helpful to explore the functional roles of AQP11 in the kidney.
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PMID:Proteomic analysis of AQP11-null kidney: Proximal tubular type polycystic kidney disease. 2920 17