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

A case of renal pelvic tumors occurring in a 44-year-old man is reported. There were two polypoid renal pelvic tumors which consisted of glandular and stromal components. Some glands in the tumors had ciliated epithelium and were quite similar to the epididymal tubules. Other glands in the tumors resembled the collecting duct or the mesonephric remnant seen in female genitalia. Immunohistochemistry and electron microscopy revealed smooth muscle differentiation of the stromal cells of these tumors. Some psammoma bodies were seen in the glands of the tumors. We diagnosed these tumors as adult mesoblastic nephroma (MN). The patient has been followed up for 14 months, showing no evidence of recurrence. Differentiation of the tumors from angiomyolipoma, leiomyoma, and nephrogenic adenofibroma is discussed. Adult renal tumors that consist of epithelial and stromal components have been reported under various names. They constitute clinicopathologically different entities originating from pediatric MN. We suggest that these tumors should be termed "adult MN".
 ...
PMID:Adult mesoblastic nephroma with ciliated epithelium. A case report. 1078 71

The kidney, epididymis, and lungs are complex organs with considerable epithelial cell heterogeneity. This has limited the characterization of pathophysiological transport processes that are specific for each cell type in these epithelia. The purpose of the present study was to develop new tools to study cell-specific gene and protein expression in such complex tissues and organs. We report the production of a transgenic mouse that expresses enhanced green fluorescent protein (EGFP) in a subset of epithelial cells that express the B1 subunit of vacuolar H(+)-ATPase (V-ATPase) and are actively involved in proton transport. A 6.5-kb portion of the V-ATPase B1 promoter was used to drive expression of EGFP. In two founders, quantitative real-time RT-PCR demonstrated expression of EGFP in kidney, epididymis, and lung. Immunofluorescence labeling using antibodies against the B1 and E subunits of V-ATPase and against carbonic anhydrase type II (CAII) revealed specific EGFP expression in all renal type A and type B intercalated cells, some renal connecting tubule cells, all epididymal narrow and clear cells, and some nonciliated airway epithelial cells. No EGFP expression was detected in collecting duct principal cells (identified using an anti-AQP2 antibody) or epididymal principal cells (negative for V-ATPase or CAII). This EGFP-expressing mouse model should prove useful in future studies of gene and protein expression and their physiological and/or developmental regulation in distinct cell types that can now be separated using fluorescence-assisted microdissection, fluorescence-activated cell sorting, and laser capture microdissection.
 ...
PMID:V-ATPase B1-subunit promoter drives expression of EGFP in intercalated cells of kidney, clear cells of epididymis and airway cells of lung in transgenic mice. 1563 43

The kidney has an important role in the regulation of acid-base homeostasis. Renal ammonium production and excretion are essential for net acid excretion under basal conditions and during metabolic acidosis. Ammonium is secreted into the urine by the collecting duct, a distal nephron segment where ammonium transport is believed to occur by non-ionic NH(3) diffusion coupled to H(+) secretion. Here we show that this process is largely dependent on the Rhesus factor Rhcg. Mice lacking Rhcg have abnormal urinary acidification due to impaired ammonium excretion on acid loading-a feature of distal renal tubular acidosis. In vitro microperfused collecting ducts of Rhcg(-/-) acid-loaded mice show reduced apical permeability to NH(3) and impaired transepithelial NH(3) transport. Furthermore, Rhcg is localized in epididymal epithelial cells and is required for normal fertility and epididymal fluid pH. We anticipate a critical role for Rhcg in ammonium handling and pH homeostasis both in the kidney and the male reproductive tract.
 ...
PMID:A role for Rhesus factor Rhcg in renal ammonium excretion and male fertility. 1902 Jun 10

The vacuolar H(+)-ATPase (V-ATPase) in type A kidney intercalated cells is a major contributor to acid excretion in the collecting duct. The mechanisms of V-ATPase-trafficking regulation in kidney intercalated cells have not been well-characterized. In developmentally related epididymal clear cells, we showed previously that PKA, acting downstream of soluble adenylyl cyclase (sAC), induces V-ATPase apical membrane accumulation. These PKA-mediated effects were inhibited by activators of the metabolic sensor AMP-activated kinase (AMPK) in clear cells. Here, we examined the regulation of V-ATPase subcellular localization in intercalated cells by PKA and AMPK in rat kidney tissue slices ex vivo. Immunofluorescence labeling of kidney slices revealed that the PKA activator N(6)-monobutyryl cAMP (6-MB-cAMP) induced V-ATPase apical membrane accumulation in collecting duct intercalated cells, whereas the V-ATPase had a more cytosolic distribution when incubated in Ringer buffer alone for 30 min. V-ATPase accumulated at the apical membrane in intercalated cells in kidney slices incubated in Ringer buffer for 75 min, an effect that was prevented by treatment with PKA inhibitor (mPKI). The V-ATPase distribution was cytosolic in intercalated cells treated with the carbonic anhydrase inhibitor acetazolamide or the sAC inhibitor KH7, effects that were overridden by 6-MB-cAMP. Preincubation of kidney slices with an AMPK activator blocked V-ATPase apical membrane accumulation induced by 6-MB-cAMP, suggesting that AMPK antagonizes cAMP/PKA effects on V-ATPase distribution. Taken together, our results suggest that in intercalated cells V-ATPase subcellular localization and therefore its activity may be coupled to acid-base status via PKA, and metabolic status via AMPK.
 ...
PMID:Vacuolar H+-ATPase apical accumulation in kidney intercalated cells is regulated by PKA and AMP-activated protein kinase. 2014 66

The vacuolar H(+)-ATPase (V-ATPase) is a major contributor to luminal acidification in epithelia of Wolffian duct origin. In both kidney-intercalated cells and epididymal clear cells, cAMP induces V-ATPase apical membrane accumulation, which is linked to proton secretion. We have shown previously that the A subunit in the cytoplasmic V(1) sector of the V-ATPase is phosphorylated by protein kinase A (PKA). Here we have identified by mass spectrometry and mutagenesis that Ser-175 is the major PKA phosphorylation site in the A subunit. Overexpression in HEK-293T cells of either a wild-type (WT) or phosphomimic Ser-175 to Asp (S175D) A subunit mutant caused increased acidification of HCO(3)(-)-containing culture medium compared with cells expressing vector alone or a PKA phosphorylation-deficient Ser-175 to Ala (S175A) mutant. Moreover, localization of the S175A A subunit mutant expressed in HEK-293T cells was more diffusely cytosolic than that of WT or S175D A subunit. Acute V-ATPase-mediated, bafilomycin-sensitive H(+) secretion was up-regulated by a specific PKA activator in HEK-293T cells expressing WT A subunit in HCO(3)(-)-free buffer. In cells expressing the S175D mutant, V-ATPase activity at the membrane was constitutively up-regulated and unresponsive to PKA activators, whereas cells expressing the S175A mutant had decreased V-ATPase activity that was unresponsive to PKA activation. Finally, Ser-175 was necessary for PKA-stimulated apical accumulation of the V-ATPase in a polarized rabbit cell line of collecting duct A-type intercalated cell characteristics (Clone C). In summary, these results indicate a novel mechanism for the regulation of V-ATPase localization and activity in kidney cells via direct PKA-dependent phosphorylation of the A subunit at Ser-175.
 ...
PMID:PKA regulates vacuolar H+-ATPase localization and activity via direct phosphorylation of the a subunit in kidney cells. 2052 92

Maintaining tight control over body fluid and acid-base homeostasis is essential for human health and is a major function of the kidney. The collecting duct is a mosaic of two cell populations that are highly specialized to perform these two distinct processes. The antidiuretic hormone vasopressin (VP) and its receptor, the V2R, play a central role in regulating the urinary concentrating mechanism by stimulating accumulation of the aquaporin 2 (AQP2) water channel in the apical membrane of collecting duct principal cells. This increases epithelial water permeability and allows osmotic water reabsorption to occur. An understanding of the basic cell biology/physiology of AQP2 regulation and trafficking has informed the development of new potential treatments for diseases such as nephrogenic diabetes insipidus, in which the VP/V2R/AQP2 signaling axis is defective. Tubule acidification due to the activation of intercalated cells is also critical to organ function, and defects lead to several pathological conditions in humans. Therefore, it is important to understand how these "professional" proton-secreting cells respond to environmental and cellular cues. Using epididymal proton-secreting cells as a model system, we identified the soluble adenylate cyclase (sAC) as a sensor that detects luminal bicarbonate and activates the vacuolar proton-pumping ATPase (V-ATPase) via cAMP to regulate tubular pH. Renal intercalated cells also express sAC and respond to cAMP by increasing proton secretion, supporting the hypothesis that sAC could function as a luminal sensor in renal tubules to regulate acid-base balance. This review summarizes recent advances in our understanding of these fundamental processes.
 ...
PMID:New insights into the dynamic regulation of water and acid-base balance by renal epithelial cells. 2246 Jul 10