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)

There are two known forms of hereditary polycystic kidney disease (PKD) in humans. Although both forms initiate early in life, autosomal recessive PKD is rapidly progressive to kidney failure shortly after birth whereas autosomal dominant PKD is slowly progressive, taking many years to end stage. Research in this field has been limited by the availability of suitable animal models of PKD. Recently the C57BL/6J-cpk mouse has been used to study the pathogenesis of rapidly progressive hereditary PKD. The study presented here describes a slowly progressive PKD in the DBA/2-pcy mouse. The disease trait is transmitted in an autosomal recessive pattern and was localized to chromosome 9 through linkage to the dilute coat color and transferrin genes. Whereas some cystic changes were seen in fetal and newborn affected mice, renal enlargement did not develop until after 8 weeks of age and azotemia did not develop until after 18 weeks of age. Renal cysts were identified in all segments of the nephron and collecting duct and progressively enlarged with age. Individual cysts were found to be lined by a single layer of epithelial cells in most areas, with focal polyps and mounds of cells principally in collecting duct cysts. Early stages of cyst formation were associated with some abnormalities of tubular and glomerular basement membranes and accelerated eruption of incisors. Late stages of the disease were characterized by azotemia and chronic renal interstitial inflammatory infiltrates in all affected animals and cerebral vascular aneurysms in a few. We conclude that the DBA/2-pcy mouse has a form of renal cystic disease that appears similar in many respects to that seen in the dominant form of human PKD.
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PMID:A hereditary model of slowly progressive polycystic kidney disease in the mouse. 188 68

Cell culture conditions were devised that selectively supported growth of 13 or 14 gestation day F344 rat ureteric bud, the renal collecting duct anlagen. These same conditions also inhibited the growth of metanephrogenic mesenchyme, precursor of structures proximal to the duct. Isolated buds were cultured in Ham's F12 medium supplemented with epidermal growth factor, selenium, insulin, hydrocortisone, prostaglandin E1, transferrin, and triiodothyronine; fetal bovine serum (1%) was required for continuous propagation. Cultured cells were epithelial in morphology and formed domes. By electron microscopy, many structural characteristics of highly differentiated cells were evident: numerous mitochondria, Golgi apparatus, extensive endoplasmic reticulum, an occasional cilium, intracytoplasmic filaments, polarized formation of microvilli, and gap junctions. Histochemistry revealed considerable functional differentiation as well. Cultured bud cells, adult collecting duct, and fetal duct anlagen were positive for acid phosphatase, membrane-localized ATPase, and nonspecific esterase. Bud cells and fetal duct anlagen expressed high levels of gamma-glutamyl transpeptidase activity while adult collecting duct exhibited slight activity. In addition, immunocytochemical observation of intermediate filament expression revealed the presence of epithelial cytokeratins but absence of mesenchymal vimentin in cultured bud cells and fetal and adult collecting ducts. These results indicate that the culture conditions described can maintain the partially differentiated fetal collecting duct anlagen in a state consistent with its embryonal derivation, and therefore may be useful in culture studies of renal differentiation.
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PMID:Selective growth in culture of fetal rat renal collecting duct anlagen. Morphologic and biochemical characterization. 286 2

Isolated human eccrine sweat glands have been microdissected into their secretory and reabsorptive components. Complete separation of these epithelia was confirmed by differential uptake of Neutral Red stain by an intermediate section of gland containing the junction between the secretory coil and the collecting duct. Primary cultures were obtained from explants of both tissues in medium RPMI-1640 or Williams E supplemented with foetal calf serum, insulin, transferrin, epidermal growth factor and hydrocortisone. The cells in the initial coil cultures had an elongated morphology while those of ductal origin were polyhedral. After 10 days both cultures were composed of polyhedral cells of varying diameter. All these morphological types were of epithelial lineage, as demonstrated by the binding of a monoclonal antibody to cytokeratin, the intermediate filament specific for epithelial cells. Outgrowth from both secretory and reabsorptive epithelia were multilayered, with plentiful desmosomal connections and an underlying basal lamina. Ultrastructural features typical of the epithelial cell types present in intact eccrine sweat glands were absent in a high proportion of the proliferating cells but domes, indicative of transepithelial active ion transport, were present in dense cultures from the reabsorptive duct. Outgrowth was also obtained from the secretory and reabsorptive epithelia of sweat glands from two cystic fibrotic patients. Since the most characteristic malfunction of cystic fibrosis is the impaired ion transport in the eccrine sweat gland, the availability of cultured epithelia should provide a useful model for study of the disease.
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PMID:The primary culture of epithelia from the secretory coil and collecting duct of normal human and cystic fibrotic eccrine sweat glands. 380 34

We established renal cell lines from definite nephron segments which were microdissected from kidneys of transgenic C57BL/6 mice, harboring the large T-antigen gene of temperature-sensitive mutant simian virus 40, pSVtsA58(ori-). Cell culture was under a humidified atmosphere of 5% CO2 in air, on collagen-coated dishes, and in RITC80-7 medium with 5% fetal bovine serum, 10 micrograms/ml transferrin, 1 microgram/ml insulin, 10 ng/ml recombinant human EGF, penicillin and streptomycin. Cell line which kept contact inhibition character was established from each segment. Cells derived from distal tubule, cortical and outer medullary collecting duct possessed their cyclic AMP response to arginine-vasopressin, like their original nephron segment. On the other hand, cells derived from terminal proximal tubules (S3 segment) formed a cobblestone-like confluent monolayer, and did not respond to arginine-vasopressin like their fresh segments. Since cisplatin, a well-known nephrotoxic substance, damages proximal tubules (especially S3) rather than collecting ducts, we assayed cell number, protein content, and ATP content of cultured S3 cells at various times after addition of 0.2 mM cisplatin. Decrease of cell number, total protein content and total ATP content of culture cells occurred after 10 h incubation with 0.2 mM cisplatin. The 50% lethal dose (LD50) of cisplatin in S3 cells was 4 x 10(-5) M after 20 h incubation and 8.5 x 10(-6) M after 40 h incubation. Outer medullary collecting duct (OMCD) cells were damaged 30% maximally after 20 h incubation with cisplatin, and LD50 in them became 2.5 x 10(-5) M after 40 h incubation. We could show that the LD50 of cisplatin in the OMCD cell line was three times higher than that in the S3 cell line. Thus, these cell lines are the first in the kidney to definite the segmental origin and to maintain some differentiated unique functions. They are valuable for studies on intrarenal site-specific actions and possible mechanisms of action of pharmacological and toxic substances.
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PMID:Cisplatin-induced toxicity in immortalized renal cell lines established from transgenic mice harboring temperature sensitive SV40 large T-antigen gene. 885 99

Aquaporin-2 (AQP2) is one of the water-channel proteins expressed in principal cells of kidney collecting ducts, where it is stored in the intracellular compartment. Previous studies have demonstrated that AQP2 vesicles constitute a distinct intracellular compartment partially overlapping with early endosomes. In this report, we performed in vitro experiments using the renal epithelial cell line, Madin-Darby canine kidney (MDCK) cells, stably expressing AQP2 (MDCK-hAQP2). In nonpolarized cells, AQP2 vesicles were scattered in the cytoplasm and did not colocalize with Golgi 58K or TGN38. Small portions of AQP2 vesicles were positive for the lysosome marker cathepsin D. An early endosome antigen (EEA1) localized around AQP2 vesicles in close proximity, suggesting involvement of the endosomal system in the trafficking of AQP2. AQP2 vesicles are distinct from other recycling molecules, such as glucose transporter 4 (GLUT4) and endocytosed transferrin. In polarized MDCK-hAQP2 cells, AQP2 vesicles were localized in the subapical recycling compartment and distinct from the Golgi apparatus, trans-Golgi network, lysosome, and early endosome in the nonstimulated state. When the cells were treated with forskolin, translocation of AQP2 to the apical membrane was observed. Washout of forskolin induced retrieval of AQP2 into the cytoplasm, and AQP2 was transiently colocalized with EEA1-positive endosomes. Then, AQP2 moved from EEA1-positive endosomes to the subapical AQP2-storage compartment, which is sensitive to wortmannin and LY294002. These results suggest that AQP2 resides in a recycling compartment at the apical side in polarized MDCK-hAQP2 cells, and its retrieval uses the apical endosomal system and the phosphatidylinositol 3-kinase-dependent pathway.
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PMID:Aquaporin-2 is retrieved to the apical storage compartment via early endosomes and phosphatidylinositol 3-kinase-dependent pathway. 1515 71

Agrin, a multidomain proteoglycan and neurotrypsin, a neuronal serine protease, are important for forming (neuromuscular) synapses. Proteolytical activity of neurotrypsin produces a C-terminal fragment of agrin, termed CAF, of approximately 22 kDA molecular size which also circulates in blood. The presence of CAF in urine suggests either glomerular filtration or secretion into urine. Blood levels of CAF have been identified as a potential novel marker of kidney function. Here we describe that several nephron segments in the mouse kidney express agrin and neutrotrypsin in addition to the localization of both protein in the glomerulum. Agrin mRNA and protein was detected in almost all nephron segments and mRNA abundance was highest in the inner medullary collecting duct. Neurotrypsin mRNA was mostly detected in the thick ascending limb of the loop of Henle, the distal convoluted tubule, and the inner medullary collecting duct. Moreover, we show that the proximal tubule absorbs injected recombinant CAF by a process shared with receptor-mediated and fluid phase endocytosis. Co-injection of CAF with recombinant human transferrin, a substrate of the receptor-mediated endocytic pathway as well as with FITC-labelled dextran (10 kDa), a marker of fluid phase endocytosis, showed partial colocalization of CAF with both markers. Further colocalization of CAF with the lysosomal marker cathepsin B suggested degradation of CAF by the lysosome in the proximal tubule. Thus, the murine kidney expresses agrin and neurotrypsin in nephron segments beyond the glomerulum. CAF is filtered by the glomerulum and is reabsorbed by endocytosis by the proximal tubule. Thus, impaired kidney function could impair glomerular clearance of CAF and thereby increase circulating CAF levels.
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PMID:The C-Terminal Fragment of Agrin (CAF), a Novel Marker of Renal Function, Is Filtered by the Kidney and Reabsorbed by the Proximal Tubule. 2738 Feb 75