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)

Family 3A mammalian liver cytochromes P450 (3A1, rat; 3A3/4, human) catalyze the 6 beta-hydroxylation of endogenous steroids and are steroid inducible. Our recent finding that A6 cells (a toad kidney epithelial cell line) contain corticosterone 6 beta-hydroxylase activity as a steroid-inducible microsomal cytochrome P450 raised the possibility that corticosterone 6 beta-hydroxylase activity in the A6 cells is catalyzed by a member of the 3A family. We found that incubation of A6 cell microsomes from dexamethasone-induced cells with antibodies against family 3A proteins specifically inhibited corticosterone 6 beta-hydroxylase activity. Microsomes from A6 cells analyzed on immunoblots developed with family 3A specific antibodies revealed immunoreactive proteins and treatment of A6 with corticosterone or dexamethasone increased the amounts of 3A immunoreactive protein(s). Furthermore, A6 RNA hybridized with 3A cDNAs on Northern blots and genomic DNA from A6 cells hybridized with a 3A cDNA on a Southern blot. Thus, toad kidney A6 cells express a family 3A P450 that is immunochemically, functionally, and genetically related to the mammalian liver 3A proteins. Prompted by these findings in amphibian kidney, we examined mammalian kidney for evidence of family 3A proteins. Immunocytochemical studies of frozen cryostat sections of normal adult rat kidney incubated with 3A1 antibody showed immunoreactivity only with collecting duct. Immunoblot analysis of human kidney microsomes found three protein bands representing 3A3/4, 3A5, and a 53-kDa Mr protein immunoreactive with human 3A antibody. An unexpected finding was the polymorphic expression of 3A3/4 in human kidney with only one of seven (14%) adult human kidneys tested expressing this protein while 3A5, a protein which is polymorphically expressed in adult human livers, was routinely present in the adult human kidney samples tested. Since human fetal liver contains a family 3A P450 we examined human fetal kidney microsomes by immunoblot analysis with human liver 3A antibody and found expression of a protein tentatively identified as 3A7. Thus, like A6 amphibian cells, family 3A P450 proteins and mRNAs are prominent, functional components in the kidney of mammals, including man.
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PMID:Expression of cytochrome P450 3A in amphibian, rat, and human kidney. 155 Mar 47

The discovery, within the last decade, of atrial natriuretic peptide (ANP), a family of peptides with natriuretic/diuretic and vasorelaxant properties, has prompted much research into the mechanisms and sites of action of ANP within the kidney. In the present study, ANP was localized in the kidneys of several mammalian species by immunohistochemical techniques 1) to identify possible sites of synthesis; 2) to compare the localization of ANP to known physiological effects; 3) to determine species differences, if any, in ANP localization; and 4) to study the development of ANP immunoreactivity in the fetal and neonatal rat kidney. Using an antibody against rat ANP, IV, ANP was localized exclusively on the proximal convoluted tubule (PCT) brush border and within intercalated cells of the outer medullary and cortical collecting tubules and ducts of adult mouse, rat, pig, monkey, and human kidneys. The development of ANP immunoreactivity paralleled the differentiation and maturation of collecting duct epithelium in rat fetal kidney. Atrial natriuretic peptide found within intercalated cells of the cortical and outer medullary collecting ducts may be the result of endogenous synthesis and, following secretion, may be available to receptors in the inner medullary collecting ducts.
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PMID:Immunohistochemical localization of atrial natriuretic peptide in the developing and adult mammalian kidney. 182 5

The current study was undertaken to examine and characterize junctional complexes, through freeze-fracture, in developing human fetal kidney and in cultured renal explants maturing in vitro. Tissue specimens were cultured for 7 days in Leibovitz's L-15 medium in the absence of serum or hormones. In uncultured explants, cells in the different nephron segments were joined by zonulae occludentes which consisted of ridges on the P-face and grooves on the E-face of lateral membranes. Tight junction composition was heterogeneous and complexity increased from proximal to collecting tubules. Proximal tubule cells were also characterized by the presence of gap junctions and a brush border. Podocytes were joined by macular junctions, while zipper-like junctions were observed between collecting duct cells. Intercalated cells were decorated with rod-shaped intramembrane particles on lateral and apical membranes, instead of the usual spherical particles present in other cells. All these structures could be observed at various intervals during tissue culture, indicating the preservation of ultrastructural integrity of the explants. These observations extend and support previous studies made at the light and electron microscopic levels. Thence, the present culture model constitutes a valuable tool to study the direct effect of growth factors on nephrogenesis.
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PMID:Freeze-fracture observations on human fetal kidney in serum-free organ culture. 186 1

Several steroid hormones act in the kidney. We have examined, by autoradiography, the precise distribution of receptors for aldosterone, glucocorticoids, vitamin D (1-25(OH)2D3) and estrogens, in the different epithelia of the nephron isolated by microdissection. Specific nuclear binding sites are localized in the distal parts of the nephron, with some variations according to the steroid hormone considered: target cells for aldosterone are located in the distal tubule and cortical collecting duct, glucocorticoid receptors are present in all distal segments, whereas those of 1-25(OH)2D3 are restricted to the thick ascending limb of Henle's loop and to the medullary collecting tubule. Thus, it appears that several receptors coexist in some cell types. No specific nuclear binding sites for estrogens could be detected along the nephron. On the other hand, a non nuclear specific binding for glucocorticoids was observed in the proximal tubule, where specific glucocorticoid effects have been described. By autoradiography on intact target cells, it appeared that aldosterone receptors are essentially (or exclusively) located in nuclei, as was recently described for other steroid hormones. Binding sites for aldosterone are already present in its target cells in the fetal kidney before their functional differentiation. Aldosterone is weakly metabolized in the kidney, without specific tubular localization. It is possible to show some modifications of aldosterone binding sites, at the level of its target cells, in some pathological states, such as hypertension.
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PMID:[Receptors of steroid hormones in the kidney]. 304 46

Vascular endothelial growth factor (VEGF) may modulate vascular permeability, chemotaxis for monocytes, and protease activity. In addition, VEGF may play a role in embryonic and tumor angiogenesis. In fetal mouse kidney, VEGF mRNA and protein expression have been demonstrated. This finding led to the hypothesis that VEGF might be involved in renal growth and development. To further elucidate the role of VEGF in human kidney, expression of VEGF and its receptors, the specific tyrosine kinase receptors, fit-1 and KDR, were studied. In fetal (6-24 gestational wk; mesonephros and metanephros) and adult kidney, VEGF mRNA and protein could be colocalized in glomerular epithelia and collecting duct cells by in situ hybridization and immunohistology. By reverse transcription-polymerase chain reaction, mRNA of three VEGF isoforms, VEGF121, VEGF165, and VEGF189, were found in fetal kidney and cortex, isolated glomeruli, and medulla of adult human kidney. KDR and flt-1 mRNA were coexpressed in endothelia of glomeruli and in peritubular capillaries in fetal and adult kidney. These data support the assumption that VEGF and its receptors may influence renal ontogenesis. We speculate that the constitutive expression of VEGF in adult kidney may be required for the function of VEGF receptor positive-fenestrated endothelia in glomeruli and postglomerular vessels. The expression of VEGF in collecting duct and of its receptors in medullary capillaries may in addition be relevant for maintaining medullary osmolality.
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PMID:Expression of vascular endothelial growth factor and its receptors in human renal ontogenesis and in adult kidney. 786 62

Intercalated cells are present in both the collecting duct, which is derived from the ureteric bud, and the connecting tubule (CNT), which is part of the nephron and thus is developed from the metanephric blastema. However, the embryologic origin of the intercalated cells has not been established. Two populations of intercalated cells, type A and type B, exist in the CNT and the cortical collecting duct (CCD). It is uncertain, however, whether these cells represent truly distinct cell types or whether one is derived from the other. In this study we have used specific antibodies to carbonic anhydrase II (CA II), H(+)-adenosinetriphosphatase (H(+)-ATPase), and band 3 protein to identify subpopulations of intercalated cells, to determine the site and time of their appearance, and to follow their differentiation in the developing rat kidney. Prenatal kidneys from 16-, 17-, 18-, and 20-day-old fetuses, and postnatal kidneys from 0-, 3-, 7-, 14-, and 21-day-old pups were preserved for immunohistochemical studies. Immunostaining for CA II and H(+)-ATPase appeared simultaneously in a subpopulation of cells in the CNT and the medullary collecting duct (MCD) of the 18-day-old fetus, suggesting that intercalated cells differentiate from separate foci, one in the nephron and one in the collecting duct. Cells with apical and cells with basolateral labeling for H(+)-ATPase appeared in the CNT and MCD at 18 days of gestation, indicating that type A and type B cells differentiate simultaneously during renal development. Band 3 immunostaining was very weak in the fetal kidney, but a striking increase in labeling was observed in the 3-day-old kidney, suggesting that there is an activation of acid-secreting cells shortly after birth. In the fetal kidney, immunostaining for CA II and H(+)-ATPase was observed in cells throughout the MCD and on the papillary surface. After birth, immunostaining gradually disappeared from both the papillary surface and the terminal inner MCD, and cells with basolateral labeling for H(+)-ATPase gradually disappeared from the outer MCD. The results of this study suggest that type A and type B intercalated cells represent distinct cell types that derive from undifferentiated cells at two separate foci, one in the nephron and one in the collecting duct. Our results also suggest that entire populations of intercalated cells are eliminated from the collecting duct during normal renal development.
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PMID:Differentiation of intercalated cells in developing rat kidney: an immunohistochemical study. 802 77

CAM expression was investigated immunohistochemically in tissue sections and in pure cultures of human proximal and distal tubular cells. In the fetal kidney, N-CAM immunoreactivity was detected in the non-induced and condensing metanephrogenic mesenchyme, and in all stages until the S-shaped bodies. A-CAM (N-cadherin) first appeared in the non-induced mesenchyme and remained present thereafter. Its expression became exclusively associated with the lower limb of the S-shaped bodies and the developing proximal tubule. In contrast, L-CAM (E-cadherin; uvomorulin) staining was observed in the fetal collecting duct, the upper limb of the S-shaped bodies, and the developing distal tubule. This segment-specific expression of A-CAM and L-CAM in the early developing nephron was maintained in the adult kidney: A-CAM staining was restricted to adherens junctions in the proximal tubule and thin limb, whereas L-CAM was expressed in Bowman's capsule and in all tubular segments except the proximal convoluted and straight tubule. Also after in vitro culture, A-CAM expression was an exclusive property of proximal tubular cells, while L-CAM was confined to distal tubular cells. In conclusion, each major subdivision of the fetal and adult nephron displays a characteristic combination of L-CAM and A-CAM, suggesting that they may be the basis of segmental differentiation and border formation between adjacent nephron segments.
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PMID:Stage- and segment-specific expression of cell-adhesion molecules N-CAM, A-CAM, and L-CAM in the kidney. 835 56

The distribution of epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), and EGF/TGF alpha receptor were studied by means of immunohistochemical methods starting from the very early stages of human embryonic kidney development. Mesonephros and metanephros were examined in order to detect immunoreactive staining in serial sectioned embryos and fetal kidneys. Anti-EGF immunoprecipitates were found in the S-shaped mesonephric vesicles of 6-week old embryos as well as in the mesonephric duct albeit with a lower degree of reactivity. Intense reactivity was observed in the metanephros within the blastemic caps of the same gestational period; the reaction was weaker within the ureteric bud branches. Bowman's capsule, proximal tubules, and collecting ducts were also reactive in the fetal kidney to varying degrees. The distribution of TGF alpha reactivity in the mesonephros was similar to that observed for EGF but with a lower intensity. In contrast, there was no reactivity in the metanephros, at least during the embyronic periods examined. By the 11th week of gestation, an intense reactivity for TGF alpha polipeptide was shown in the fetal kidney at the level of the proximal tubules and Bowman's capsule; distal tubules as well as all urinary structures from the collecting ducts to the pelvis were less reactive. Finally, EGF/TGF alpha receptor reactivity was identified by the 6th week of development, being more intense in the mesonephros at the level of the mesonephric duct cells. In the metanephros, the ureteric bud-derived branches were reactive, whereas most of the blastemic tissue did not stain. By the 11th week, only the collecting ducts and the remaining urinary structures contained reaction products: Reactivity was distributed to the tissues originating from the ureteric bud branching. Taking into account recent advances in knowledge about the biology of growth factors, the hypothesis is proposed that the secretory components (vesicles, glomerulus, and tubules) of renal anlagen might release the growth factors while the cells of the urinary tract (i.e., collecting duct, pelvis, etc.) may be their targets.
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PMID:Immunohistochemical localization of the epidermal growth factor, transforming growth factor alpha, and their receptor in the human mesonephros and metanephros. 889 79

The type 1 and type 2 isoforms of human 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) play a crucial role, respectively, in modulating glucocorticoid and mineralocorticoid hormone action. Deficiency of the 11 beta-HSD2 isoform, as described in the syndrome of apparent mineralocorticoid excess and following liquorice (glycyrrhetinic acid) or carbenoxolone ingestion, results in hypertension in which cortisol acts as a potent mineralocorticoid. Several studies have addressed the effects of progesterone, glycyrrhetinic acid, and their derivatives on 11 beta-HSD activity, but these were largely undertaken before the characterization of the 11 beta-HSD isoforms. The aim of this study was to evaluate the localization of 11 beta-HSD2 in human kidney and to study the effects of progesterone, glycyrrhetinic acid, and their related compounds on stable transfectants of the human 11 beta-HSD isoforms. Using an in-house sheep antibody against human 11 beta-HSD2, immunoperoxidase studies localized 11 beta-HSD2 to renal cortical and medullary collecting ducts. Glomeruli, vascular structures, loops of Henle, and proximal tubules were all negative. Confocal laser microscopy studies indicated both a cytoplasmic and nuclear localization for the enzyme within renal collecting ducts. The nuclear staining, which was intranuclear and was not associated with the nuclear membrane, accounted for 40% of the total cellular 11 beta-HSD2 immunoreactivity. Kinetic analysis of 11 beta-HSD activity in fetal kidney 293 cells stably transfected with h11 beta-HSD1/pcDNA3 or 11 beta-HSD2/pCR3, indicated, respectively, low-affinity dehydrogenase/oxoreductase activity (Km for F, 1.8 microM; Km for E, 270 nM) and high-affinity dehydrogenase activity (Km for F, 190 nM). The reductase activity of 11 beta-HSD1 was inhibited by 11 alpha-hydroxyprogesterone > carbenoxolone = glycyrrhetinic acid = progesterone > 11 beta-hydroxyprogesterone. The dehydrogenase activity of 11 beta-HSD2 was inhibited 11 alpha-hydroxyprogesterone = 11 beta-hydroxyprogesterone > glycyrrhetinic acid > carbenoxolone = progesterone. 11 beta-HSD2, expressed in the renal collecting duct, serves to protect the mineralocorticoid receptor (MR) in an autocrine fashion. The demonstration of a nuclear localization for what was thought to be principally a microsomal enzyme suggests that interaction between the MR and its ligand (either aldosterone or cortisol) may be a nuclear rather than a cytoplasmic event. The inhibitory effects of progesterone, glycyrrhetinic acid, and related compounds on 11 beta-HSD1 and 2 were similar, and it remains to be seen what implication these findings have for 11 beta-HSD1 action in tissues such as the liver and gonad and renal 11 beta-HSD2 activity in relation to sodium homeostasis and blood pressure control.
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PMID:Human 11 beta-hydroxysteroid dehydrogenase: studies on the stably transfected isoforms and localization of the type 2 isozyme within renal tissue. 902 19

To gain insight into the roles of cyclooxygenase (COX)-1 and -2 in human kidney, we analyzed their expressions and localization in adult and fetal normal kidney. Immunohistology showed expression of COX-1 in collecting duct cells, interstitial cells, endothelial cells, and smooth muscle cells of pre- and postglomerular vessels. Expression of COX-2 immunoreactive protein could be localized to endothelial and smooth muscle cells of arteries and veins and intraglomerularly in podocytes. In contrast to the rat, COX isoforms were not detected in the macula densa. These data were confirmed by in situ mRNA analysis using digoxigenin-labeled riboprobes. In fetal kidney, COX-1 was primarily expressed in podocytes and collecting duct cells. Expression levels of COX-1 in both cell types increased markedly from subcapsular to juxtamedullary cortex. Glomerular staining of COX-2 was detectable in podocytes only at the endstage of renal development. In summary, the localization of COX-2 suggests that this enzyme may be primarily involved in the regulation of renal perfusion and glomerular hemodynamics. The expression of COX-1 in podocytes of the fetal kidney and its absence in adult glomeruli suggests that this isoform might be involved in glomerulogenesis.
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PMID:Localization of cyclooxygenase-1 and -2 in adult and fetal human kidney: implication for renal function. 914 46


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