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The Journal of Clinical Endocrinology & Metabolism Vol. 87, No. 2 877-882
Copyright © 2002 by The Endocrine Society

Other Original Articles

11ß-Hydroxysteroid Dehydrogenase Type 2 Is Expressed in the Human Kidney Glomerulus

Saeko Kataoka, Akihiko Kudo, Hiroshi Hirano, Hayato Kawakami, Toshio Kawano, Eiji Higashihara, Hirotoshi Tanaka, Francoise Delarue, Jean-Daniel Sraer, Tomoatsu Mune, Zygmunt S. Krozowski and Kunimasa Yan

Departments of Pediatrics, Kyorin University School of Medicine (S.K., T.K., K.Y.), Anatomy (A.K., H.H., H.K.), and Urology (E.H.), Kyorin University School of Medicine, Tokyo 181-8611, Japan; Department of Clinical Immunology and AIDS Research Center Institute of Medical Science (H.T.), University of Tokyo 108-8639, Tokyo, Japan; INSERM, U-64, Hospital Tenon (F.D., J.-D.S.), Paris 75020, France; Third Department of Internal Medicine, Gifu University School of Medicine (T.M.), Gifu 500-8705, Japan; and Molecular Hypertension Laboratory, Baker Medical Research Institute (Z.S.K.), Melbourne 8008, Australia

Address all correspondence and requests for reprints to: Dr. Kunimasa Yan, Department of Pediatrics, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan. E-mail: pmeneki{at}kyorin-u.ac.jp

Abstract

Our previous study demonstrated that the GR is expressed in the human kidney glomerulus. The function of the GR of glomerular cells might be affected by the concentration of intracellular glucocorticoids, which is modulated by 11ß-hydroxysteroid dehydrogenase type 2 (11ßHSD2). Because the expression of 11ßHSD2 in the glomerular cells remains unclear, we used competitive RT-PCR and immunoblotting to detect the expression of 11ßHSD2 mRNA and protein in isolated human glomeruli, in whole kidney cortex as a positive control, and in a human glomerular visceral epithelial cell line. 11ßHSD2 mRNA was detected in all samples. Specific antihuman 11ßHSD2 antibody recognized a single band at 41 kDa, consistent with the molecular mass of human 11ßHSD2, in the samples of the isolated glomeruli and whole kidney cortex. Furthermore, definite 11ßHSD2 enzymatic activity was also determined with the sample of isolated glomeruli.

We also performed immunohistochemistry by light and electron microscopy to determine the cellular and subcellular localization of 11ßHSD2 in the human glomeruli. Immunoreactivity of the enzyme was clearly observed in the glomerular visceral epithelial cells and endothelial cells as well as in the distal convoluted tubules and collecting ducts. The subcellular localization of 11ßHSD2 was shown to be endoplasmic reticulum. These results suggest that 11ßHSD2 might play a crucial role in modulating the intracellular concentration of glucocorticoids in human glomerular cells.

SYNTHETIC GLUCOCORTICOIDS have been widely used and are known to have therapeutic effects to resolve proteinuria in various glomerular diseases (1, 2); however, the precise mechanisms of its antiproteinuric effect remain unclear. Many glomerular diseases are initiated by an immune response, which may be humoral or cell mediated, against either exogenous or native antigens, with the result being glomerular cell injury (3, 4, 5, 6). Therefore, both peripheral blood-derived activated cells and injured glomerular cells themselves can be the target cells of synthetic glucocorticoids.

In a previous paper we reported that normal human kidney glomerular cells distinctly express GR that undergo nuclear translocation after binding to synthetic glucocorticoid (7). This suggested that human glomeruli should be one of the targets of synthetic glucocorticoids, acting via the GR. Elucidation of the mechanisms affording GR function in the glomerulus is essential to ascertain the reason for altered glucocorticoid sensitivity in various glomerular diseases. GR function can be potentially enhanced or limited by regulation of the local concentration of intracellular glucocorticoids, where concentration is modulated by the 11ßHSD enzymes (8).

To date, two distinct forms have been recognized. The NADP-dependent 11ßHSD isoform, named type 1, works bidirectionally, oxidizing and reducing physiological glucocorticoids (9). On the other hand, the NAD-dependent 11ßHSD isoform, named type 2 (11ßHSD2), potently inactivates glucocorticoids (10, 11). Recently, the localization of 11ßHSD isoforms in various tissues has been intensively investigated. In the rodent kidney, 11ßHSD1 was only detected in proximal tubules in the cortex and in interstitial cells within the medulla (12, 13). As the human kidney has only a barely detectable level of 11ßHSD1 (14), its localization is still unknown. In contrast, specific purified antibody against human 11ßHSD2 recognized the intense immunoreactivity in collecting ducts and distal convoluted tubules of the human kidney (15, 16, 17, 18); the enzyme was also detected in the glomerulus, where a faint signal was observed in some glomerular visceral epithelial cells (15, 16).

Confirmation that the human kidney glomerulus expresses 11ßHSD2 would contribute to analysis of the mechanism of synthetic glucocorticoid action via the GR in the human kidney glomerulus. Therefore, in the present study we sought to prove the existence of 11ßHSD2 mRNA, protein, and activity in the human glomerulus using freshly isolated human glomeruli. Further, immunohistochemistry by light microscopy and electron microscopy was performed to determine the cellular and subcellular localization of 11ßHSD2 in human glomeruli of the normal kidney cortex.

Materials and Methods

Samples

Four human kidney cortex samples were obtained from histologically normal regions of fresh kidneys of surgical specimens from patients undergoing nephrectomy with renal cancer or ureter cancer at Kyorin University Hospital. The glomeruli were isolated from human kidney cortex by a differential sieving technique (7). The purity of the preparation, as assessed by phase contrast microscopy, was greater than 95%.

Human glomerular visceral epithelial cells (HGVE) were cultured in DMEM/F-12 medium (Life Technologies, Inc., Grand Island, NY) supplemented with antibiotics and 3 x 108 M sodium selenite (Life Technologies, Inc.), 5 µg/ml insulin (Sigma, St. Louis, MO), 5 µg/ml transferrin (Life Technologies, Inc.), and 1% FCS (Life Technologies, Inc.) in a humidified atmosphere at 37 C and containing 5% CO2 (19, 20).

Measurement of abundance of 11ßHSD2 and 11ßHSD1 mRNA by competitive RT-PCR

We employed quantitative competitive RT-PCR to measure the mRNA levels of 11ßHSD2 and 11ßHSD1. Further, the mRNA values were normalized for glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a housekeeping gene, to minimize the variations in deoxyribonuclease digestion and RT between samples. Total RNA was extracted from the isolated glomeruli, cultured HGVE cells, and whole kidney cortex using Isogen (Wako Life Science Reagents, Osaka, Japan) according to the manufacturer’s protocol, and 0.65 µg total RNA was treated with deoxyribonuclease I (Life Technologies, Inc., Gaithersburg, MD) and reverse transcribed with 240 U Superscript II reverse transcriptase (Life Technologies, Inc.) in a 30-µl reaction volume containing 2.5 mM random 9-mer, 1 mM of each dNTP, 8 U placental ribonuclease inhibitor, and the manufacturer’s buffer. Each reaction was allowed to proceed at room temperature for 10–15 min, followed by incubation at 42 C for 1.5 h. Competitors for each cDNA were prepared following the PCR MIMIC KIT protocol (CLONTECH Laboratories, Inc., Palo Alto, CA). Gene-specific primers for each cDNA are as follows; 11ßHSD1 (21), 5'-GAC ATG CTC ATT CTC AA-3' (sense, nucleotides 558–579) and 5'-GCT GTT TCT GTG TCT CTA TGA-3' (antisense, nucleotides 868–889); 11ßHSD2 (22), 5'-GCT GCT GCA GAT GGA CCT-3' (sense, nucleotides 98–117) and 5'-GCA GCC AGG CTG GAT GAT G-3' (antisense, nucleotides 446–465); and GAPDH (23), 5'-TCA TCA TCT CTG CCC CCT CTG CTG-3' (sense, nucleotides 482–497) and 5'-GAC GCC TGC TTC ACC ACC TTC TTG-3' (antisense, nucleotides 812–832). Quantitative competitive PCR was performed by addition of 2.5 pmol of a sense and an antisense primer to 0.5 µl reverse transcribed samples with 0.5 µl of various ranges of 2.5 times serially diluted competitor in 5 µl of a previously described (24) PCR buffer (2.5 mM Mg2+) and 0.25 U Ex Taq DNA polymerase (TaKaRa Co., Osaka, Japan) for 11ßHSD1 and 11ßHSD2. For GAPDH, 2 mM Mg2+ and 5% glycerol were used. Samples were subjected to initial denaturation at 96 C for 2 min, followed by 35–50 cycles of 96 C denaturation for 20 sec, 62 C annealing for 20 sec, and 72 C extension for 30 sec. PCR products were subjected to electrophoresis in 2.5% agarose gels and stained with ethidium bromide. Gels were loaded into a Macintosh computer with a DC120 digital camera (Eastman Kodak Co., Rochester, NY). The band intensities were analyzed using NIH Image 1.60 (Rasband W), and the amount of the competitor whose intensity was equal to the intrinsic template was calculated as the corresponding mRNA level by linear regression.

Measurement of 11ßHSD2 activity in the isolated glomeruli

Immediately after thawing, the isolated glomeruli were homogenized on ice with a Dounce homogenizer (Kontes Co., Vineland, NJ) in the homogenizing buffer (50 mM Tris-HCl, 0.25 M sucrose, 2 mM EDTA, 1 mM MgCl2, and 1 mM dithiothreitol, pH 7.4) containing 2 µg/ml aprotinin, 2 µg/ml leupeptin, and 100 µg/ml phenylmethylsulfonylfluoride. After brief sonication, lysates were centrifuged at 800 x g for 10 min to separate nuclei. The protein concentration was determined using the DC protein assay kit (Bio-Rad Laboratories, Inc., Hercules, CA). NAD+-dependent 11ß-dehydrogenase activity was assessed by incubating 100 µg protein of nuclei or 800 µg supernatant fractions for 6 h at 37 C in 500 µl assay buffer (50 mM Tris-HCl, 2 mM EDTA, 1 mM MgCl2, 1 mM dithiothreitol, 20% glycerol, and 0.4 mM NAD+, pH 7.4) with 2.4 or 5.3 nM 3H-labeled steroid and 10 or 50 nM unlabeled steroid (corticosterone or cortisol, respectively). The reactions were terminated by adding 3 ml dichloromethane, and extracted steroids were separated on TLC plates (Whatman, Clifton, NJ) using dichloromethane-acetone (82:18 or 75:25) as mobile phases. The fractional conversion of corticosterone or cortisol to 11-dehydrocorticosterone or cortisone, respectively, was determined. The mean of tetraplicates was used, and enzyme activities were expressed as the percent conversion per h/mg protein.

Immunoblotting

Immunoblotting was performed as previously described (7). Briefly, samples of kidney cortex, freshly isolated glomeruli, and HGVE cells were separated by 10% SDS-PAGE under reducing conditions and transferred to nitrocellulose filters. After blocking nonspecific sites, the nitrocellulose blot was incubated overnight at 4 C with purified antihuman 11ßHSD2 polyclonal antibody (HUH23) at a concentration of 0.25 µg/ml, diluted by washing buffer [10 mM Tris-HCl (pH 7.4) containing 1% nonfat dry milk and 0.05% Tween 20]. The specificity of HUH23 antibody was previously reported (15, 16, 18). The filter was then incubated at room temperature for 60 min with a 1:1000 dilution of goat antirabbit antibody conjugated to horseradish peroxidase. The blot was washed and developed using a chemiluminescence kit (NEN, Boston, MA) according to the manufacturer’s instructions.

Light microscopy

Fresh kidney cortex samples were fixed in 4% formaldehyde-0.1 M PBS for 6 h at 4 C; immersed in 5%, 10%, and 20% sucrose-PBS; and embedded in OCT compound (Sakura Finetechnical Co., Tokyo, Japan). These samples were cut into serial 10-µm thick sections for immunohistochemistry. After having been incubated with blocking buffer (2% BSA, 5% goat serum, and 0.05% Tween 20 in PBS) for 30 min at room temperature, the slides were reacted with HUH23 or normal rabbit IgG overnight at 4 C at a concentration of 4 µg/ml in blocking buffer. After three washes with PBS containing 0.05% Tween 20 (PBS-Tween), the slides were incubated for 30 min with 0.6% H2O2/methanol to quench endogenous peroxidase activity. After a further wash in PBS, the slides were incubated for 1 h at room temperature with horseradish peroxidase-labeled dextran polymer-conjugated goat antirabbit antibody (EnVison system, DAKO Corp., Kyoto, Japan) as a secondary antibody. Then the slides were washed in PBS-Tween and developed by immersion in 1.4 mM 3,3'-diaminobenzidene tetrahydrochloride (Sigma, St. Louis, MO) in PBS for 10 min at room temperature. After a final washing in PBS, the slides were mounted in Permount (Muto Pure Chemicals, Ltd., Tokyo, Japan).

Immunoelectron microscopy

Immunostaining of 11ßHSD2 in frozen sections was performed as described above, and the sections were prepared for immunoelectron microscopic examination by employing the preembedding procedure (25). Briefly, after 3,3'-diaminobenzidene tetrahydrochloride-H2O2 treatment, the sections were treated with 1% osmium tetraoxide in 0.1 M phosphate buffer for 10 min, dehydrated by passage through a series of graded ethanols, and embedded in Epon on glass slides. Ultrathin sections were made, stained with 0.1% lead citrate for 7 min, and examined at 80 kV with a transmission election microscope (JEM-1010, JEOL USA, Inc., Tokyo, Japan).

Results

To estimate the amount of 11ßHSD2 mRNA in the human glomeruli, we employed a quantitative competitive RT-PCR. As shown in Fig. 1Go, levels of 11ßHSD2 mRNA (expressed as the ratio of 11ßHSD2/GAPDH) were 0.263 in isolated glomeruli, approximately 3 times higher than the expression levels in whole kidney cortex (mean ± SE, 0.082 ± 0.008; n = 5) (26), and 0.011 in HGVE. In contrast, levels of 11ßHSD1 mRNA (the ratio of 11ßHSD1/GAPDH) were 0.0012 in isolated glomeruli and 0.0015 in HGVE, which were lower than the expression levels in whole kidney cortex (0.027 ± 0.013). In isolated glomeruli, NAD+-dependent 11ß-dehydrogenase activity, assumed to be 11ßHSD2 activity, was 1.32 ± 0.21% conversion/h·mg protein in supernatant and 3.72 ± 0.08 in nuclei with cortisol as a substrate. Corticosterone, although not the most physiologically important glucocorticoid in humans, is a better substrate for the enzyme, and the 11ß-dehydrogenase activity with corticosterone as a substrate was 8.18 ± 0.30% conversion/h·mg in supernatant and 18.76 ± 0.97 in nuclei. However, no detectable NAD+- dependent 11ß-dehydrogenase activity was demonstrated in lysates of HGVE (data not shown). In addition, to demonstrate the presence of 11ßHSD2 protein in the glomerulus, we performed immunoblotting using HUH23 antibody. As shown in Fig. 2Go, the HUH23 antibody clearly detected a single band at 41 kDa with samples of freshly isolated human glomeruli as well as whole kidney cortex. We conclude that 11ßHSD2 is expressed not only in distal convoluted tubules and collecting ducts, but also in the glomeruli of the human kidney.



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  		Figure 1. Representatives of competitive RT-PCR for GAPDH and 11ßHSD2 mRNA. The upper bands are competitors, and the lower bands are endogenous products. Gl, Freshly isolated human glomeruli. The concentration of each competitor is denoted between each figure with units of 10-3 x attomol/reverse transcribed sample derived from 0.015 µg total RNA. Each competitor was diluted serially by 2.5-fold.

 


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  		Figure 2. Immunoblotting of 11ßHSD2 in whole kidney cortex and freshly isolated glomeruli. Lane 1, Protein extracts (100 µg) from whole kidney cortex (positive control). Lane 2, Protein extracts (100 µg) from freshly isolated glomeruli. The positions of molecular mass markers are shown at the left. Both samples indicate the band of 41-kDa protein.

 
We performed further immunohistochemical studies to determine the localization of 11ßHSD2 protein in the human kidney glomerulus. When human kidney sections were incubated with HUH23 antibody, intense immunoreactivity was observed in distal convoluted tubules and collecting ducts, where the reactivity seemed to be localized in the cytoplasm (Fig. 3AGo). In addition, the HUH23 antibody detected moderate immunoreactivity in the glomeruli and proximal tubules. The specificity of this reaction was confirmed by the use of nonimmune rabbit IgG instead of HUH23 antibody (Fig. 3BGo). At the higher magnification, the glomerulus showed marked immunostaining in the cytoplasm of visceral epithelial cells, but not in parietal cells (Fig. 3CGo). The subcellular localization of 11ßHSD2 in the human kidney was also determined by immunoelectron microscopy. In distal convoluted tubules, strong immunostaining of 11ßHSD2 enzyme was diffusely distributed in the cytoplasm, not in the nucleus (Fig. 4AGo). Specificity was again confirmed by the use of nonimmune rabbit IgG (Fig. 4BGo). In the glomerulus, immunoreactivity was evident as dark staining in the cytoplasm of glomerular visceral epithelial cells, but no enzyme was detected in the mesangial cells (Fig. 4CGo). Nonimmune rabbit IgG did not show positive immunoreactivity (Fig. 4DGo). Reactivity was consistent with an endoplasmic reticulum staining pattern (Fig. 4EGo). Interestingly, glomerular endothelial cells were also found to contain the 11ßHSD2 enzyme (Fig. 4FGo).



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  		Figure 3. Light microscopic observation of 11ßHSD2 protein in kidney cortex. A, Kidney cortex staining with 11ßHSD2. Magnification, x220. Bar, 50 µm. B, Kidney cortex staining with nonimmune rabbit IgG. Magnification, x220. Bar, 50 µm. C, Higher magnification of glomerulus staining with 11ßHSD2. Magnification, x900. Bar, 10 µm. G, Glomerulus; P, proximal convoluted tubule; D, distal convoluted tubule; arrowheads, nuclei of visceral epithelial cells; asterisks, capillary lumens.

 


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  		Figure 4. Immunoelectron microscopic localization of 11ßHSD2 protein in glomerulus. A and B, Distal convoluted tubule reacted with anti-11ßHSD2 antibody, HUH23 (magnification of A, x4,600) and with nonimmune rabbit IgG (magnification of B, x3,200). Bar, 2 µm. C and D, Low magnification of glomerulus reacted with HUH23 (magnification of C, x5,000) and with nonimmune rabbit IgG (magnification of D, x5,000.). Bar, 2 µm. E, 11ßHSD2-positive immunostaining in visceral epithelial cell indicates the endoplasmic reticulum staining pattern in cytoplasm (arrowhead). Magnification, x17,000. Bar, 0.5 µm. F, 11ßHSD2-positive immunostaining in glomerular endothelial cell indicates more sparse distribution in cytoplasm than visceral epithelial cell. Magnification, x7,800. Bar, 2 µm. Ep, Visceral epithelial cell; En, glomerular endothelial cell; M, mesangial cell; N, nucleus; arrowheads, positive staining of endoplasmic reticulum.

 
Discussion

The modulation of intracellular concentrations of endogenous and synthetic glucocorticoids is an important mechanism regulating GR occupation at a prereceptor level in the human glomerulus. Two 11ßHSD isoforms have been proposed as the key molecules to control the intracellular concentration of glucocorticoids. In this study we have focused on 11ßHSD2 and addressed the question of whether the human kidney glomeruli distinctly express this isoform. To determine the existence of 11ßHSD2 of the human glomeruli, we examined the abundance of its mRNA expression in the freshly isolated human glomeruli. This isolation method gave a purity greater than 95% (7). As the samples for quantitative competitive RT-PCR analysis, we used isolated glomeruli, kidney whole cortex as a positive control, and HGVE cells because the previous localization study suggested the existence of 11ßHSD2 in glomerular visceral epithelial cells (15, 16). The mRNA level of 11ßHSD2 in the human glomerulus was higher than that in kidney whole cortex, and NAD+-dependent 11ß-dehydrogenase activity was confirmed. Additionally, in the immunoblotting using specific antibody against human 11ßHSD2, we could detect a single band corresponding to a molecular mass of 41 kDa in the samples of both isolated glomeruli as well as whole kidney cortex. Thus, we concluded unequivocally that the human glomeruli express the functional 11ßHSD2 enzyme. The sample of HGVE cells had 11ßHSD2 mRNA with much lower levels than the glomeruli or whole cortex and did not show the positive immunoproduct of 11ßHSD2 in the immunoblotting. It is possible that this cell line might express a very low level of 11ßHSD2 protein under the conditions of cell culture we used.

There have been conflicting results regarding the localization of 11ßHSD2 enzyme in the human kidney glomerulus (15, 16, 17, 18). To increase the sensitivity of immunostaining, in the present study we used dextran polymer-conjugated secondary antibody (EnVision system) as described previously (7). The results provided clear evidence of the localization of this isoform in glomerulus as well as distal convoluted tubules and collecting ducts. In glomerulus, light microscopic examination suggested a visceral epithelial pattern for the localization of 11ßHSD2 enzyme. However, when the immunostaining of 11ßHSD2 was observed by electron microscopy, interestingly, the glomerular endothelial cells were also found to express 11ßHSD2 enzyme. These conflicting findings between light microscopy and electron microscopy might be explained by the different size of the cell body, which is much smaller for the glomerular endothelial cell than for the visceral epithelial cell. The subcellular localization of 11ßHSD2 in both cells was the same, i.e. the enzyme resided in the endoplasmic reticulum. This specific subcellular localization is consistent with earlier evidence indicating 11ßHSD2 to be a microsomal, endoplasmic reticulum-associated protein (27).

Many investigators have proposed that 11ßHSD2 is a key enzyme protecting the MR from occupation by the high circulating levels of glucocorticoids in mineralocorticoid target organs (8). However, previous localization studies showed that the MR was not present in human (18, 28) and rabbit (29) kidney glomerulus. On the other hand, the distribution of 11ßHSD2 in the glomerulus seemed to be basically the same as that of the GR described previously (7), although we could not detect expression of the enzyme in mesangial cells, which might express an extremely low level. Furthermore, in human fetal kidney, the expression of 11ßHSD2 mRNA was closely related to that of GR, not to that of MR, in the glomerulus, suggesting that 11ßHSD2 principally serves to regulate exposure of the GR to cortisol (30). In terms of synthetic glucocorticoid action, it should be noted that 11ßHSD2 has been shown to act as an oxidoreductase with dexamethasone, implying that it would enhance glucocorticoid activity (31). The physiological roles of 11ßHSD2 enzyme in the human mature kidney glomerulus should be further investigated. Furthermore, because renal 11ßHSD enzyme activity was found to increase and mRNA to decrease after glucocorticoid stimulation (32), an understanding of the regulatory system governing 11ßHSD2 enzyme activity in the glomerulus would contribute to elucidating the mechanism of altered glucocorticoid sensitivity in various glomerular diseases.

Acknowledgments

We are grateful to Ms. S. Matsubara, Mr. M. Fukuda (Laboratory for Electron Microscopy, Kyorin University School of Medicine), and Ms. T. Shibata (Department of Anatomy, Kyorin University School of Medicine) for their excellent technical assistance.

Footnotes

Abbreviations: GAPDH, Glyceraldehyde-3-phosphate dehydrogenase; HGVE, human glomerular visceral epithelial cells; 11ßHSD2, 11ß-hydroxysteroid dehydrogenase type 2.

Received May 16, 2001.

Accepted November 5, 2001.

References

  1. Tarshish P, Tobin JN, Bernstain J, Edelmann Jr CM 1997 Prognostic significance of the early course of minimal change nephrotic syndrome: Report of the International Study of Kidney Disease in Children. J Am Soc Nephrol 8:769–776[Abstract]
  2. Cattran DC, Delmore T, Roscoe J, Cole E, Cardella C, Charron R, Ritchie S 1989 A randomized controlled trial of prednisone in patients with idiopathic membranous nephropathy. N Engl J Med 320:210–215[Abstract]
  3. Couser WG 1993 Pathogenesis of glomerulonephritis. Kidney Int 42(Suppl):S19–S26
  4. Johnson RJ 1994 The glomerular response to injury: progression or resolution? Kidney Int 45:1769–1782[Medline]
  5. Yan K, Nakamura Y, Watanabe N, Kawato H, Fujimiya Y, Kohsaka T 1996 Regulation of the C3 production by gamma interferon from peripheral blood T cells in patients with membranoploriferative glomerulonephritis and poststreptococcal acute glomerulonephritis. Nephron 72:623–628[Medline]
  6. Yan K, Nakahara K, Awa S, Nishibori Y, Nakajima N, Kataoka S, Maeda M, Watanabe T, Matsushima S, Watanabe N 1998 The increase of memory T cell subsets in children with idiopathic nephrotic syndrome. Nephron 79:274–278[CrossRef][Medline]
  7. Yan K, Kudo A, Hirano H, Watanabe T, Tasaka T, Kataoka S, Nakajima N, Nishibori Y, Shibata T, Kohsaka T, Higashihara E, Tanaka H, Watanabe H, Nagasawa T, Awa S 1999 Subcellular localization of glucocorticoid receptor protein in the human kidney glomerulus. Kidney Int 56:65–73[Medline]
  8. Stewart PM, Krozowski ZS 1999 11ß-Hydroxysteroid dehydrogenase. Vitam Horm 57:249–324[Medline]
  9. Lakshmi V, Monder C 1988 Purification and characterization of the corticosteroid 11ß-dehydrogenase component of the rat liver 11ß-hydroxysteroid dehydrogenase complex. Endocrinology 123:2390–2398[Abstract/Free Full Text]
  10. Edwards CR, Stewart PM, Burt D, Brett L, McIntyre MA, Sutanto WS, de Kloet ER, Monder C 1988 Localization of 11ß-hydroxysteroid dehydrogenase-tissue specific protector of the mineralocorticoid receptor. Lancet 2:986–989[CrossRef][Medline]
  11. Funder JW, Pearce PT, Smith R, Smith AI 1988 Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated. Science 242:583–585[Abstract/Free Full Text]
  12. Castello R, Schwarting R, Muller C, Hierholzer K 1989 Immunohistochemical localization of 11ß-hydroxysteroid dehydrogenase in rat kidney with monoclonal antibody. Rev Physiol Biochem 12:320–327
  13. Rundle SE, Funder JW, Lakshmi V, Monder C 1989 The intrarenal localization of mineralocorticoid receptors and 11ß-dehydrogenase: immunocytochemical studies. Endocrinology 125:1700–1704[Abstract/Free Full Text]
  14. Nikkila H, Tannin GM, New MI, Taylor NF, Kalaitzoglou G, Monder C, White PC 1993 Defects in the HSDII gene encoding 11ß-hydroxysteroid dehydrogenase are not found in patients with apparent mineralocorticoid excess or 11-oxoreductase deficiency. J Clin Endocrinol Metab 77:687–691[Abstract]
  15. Krozowski Z, MaGuire JA, Stain-Oakley AN, Dowling J, Smith RE, Andrews RK 1995 Immunohistochemical localization of the 11ß-hydroxysteroid dehydrogenase type II enzyme in human kidney and placenta. J Clin Endocrinol Metab 80:2203–2209[Abstract]
  16. Krozowski Z, Albiston AL, Obeyesekere VR, Andrews RK, Smith RE 1995 The human 11ß-hydroxysteroid dehydrogenase type II enzyme: comparisons with other species and localization to the distal nephron. J Steroid Biochem Mol Biol 55:457–464[CrossRef][Medline]
  17. Shimojo M, Ricketts ML, Petrelli MD, Moradi P, Johnson GD, Bradwell AR, Hewison M, Howie AJ, Stewart PM 1997 Immunodetection of 11ß-hydroxysteroid dehydrogenase type 2 in human mineralocorticoid target tissues: evidence for nuclear localization. Endocrinology 138:1305–1311[Abstract/Free Full Text]
  18. Hirasawa G, Sasano H, Takahashi K, Fukushima K, Suzuki T, Hiwatashi N, Toyota T, Krozowski ZS, Nagura H 1997 Colocalization of 11ß-hydroxysteroid dehydrogenase type II and mineralocorticoid receptor in human epithelia. J Clin Endocrinol Metab 82:3859–3863[Abstract/Free Full Text]
  19. Delarue F, Virone A, Hagege J, Lacave R, Peraldi MN, Adida C, Rondeau E, Feunteun J, Sraer JD 1991 Stable cell line of T-SV40 immortalized human glomerular visceral epithelial cells. Kidney Int 40:906–912[Medline]
  20. Krishnamurti U, Chen Y, Michael A, Kim Y, Fan WW, Wieslander J, Brunmark C, Rondeau E, Sraer JD, Delarue F, Tsilibary EC 1996 Integrin-mediated interactions between primary/T-sv40 immortalized human glomerular epithelial cells and type IV collagen. Lab Invest 74:650–657[Medline]
  21. Tannin GM, Agarwal AK, Monder C, New MI, White PC 1991 The human gene for 11ß-hydroxysteroid dehydrogenase. Structure, tissue distribution, and chromosomal localization. J Biol Chem 266:16653–16658[Abstract/Free Full Text]
  22. Albiston AL, Obeyesekere VR, Smith RE, Krozowski ZS 1994 Cloning and tissue distribution of the human 11ß-hydroxysteroid dehydrogenase type 2 enzyme. Mol Cell Endocrinol 105:R11–R17
  23. Tso JY, Sun XH, Kao TH, Reece KS, Wu R 1985 Isolation and characterization of rat and human glyceraldehyde 3-phosphate dehydrogenase cDNAs: genomic complexity and molecular evolution of the gene. Nucleic Acids Res 13:2485–2502[Abstract/Free Full Text]
  24. Mune T, White PC 1996 Apparent mineralocorticoid excess: genotype is correlated with biochemical phenotype. Hypertension 27:1193–1199[Abstract/Free Full Text]
  25. Kanai Y, Kawakami H, Takata K, Kurohmaru M, Hayashi Y, Nishida T, Hirano H 1990 Localization of Forssman glycolipid and GM1 ganglioside intracellularly and on the surface of germ cells during fetal testicular and ovarian development of mice. Histochemistry 94:561–568[Medline]
  26. Mune T, Morita H, Suzuki T, Takahashi Y, Isomura Y, Tanahashi T, Daido H, Yamakita N, Deguchi T, Sasano H, White PC, Yasuda K Increased adrenal 11ß-hydroxysteroid dehydrogenase type 2 in non-functioning and preclinical Cushing’s adenoma. J Clin Endocrinol Metab, in press
  27. Naray-Fejes-Toth A, Fejes-Toth G 1996 Subcellular localization of the type 2 11ß-hydroxysteroid dehydrogenase. A green fluorescent protein study. J Biol Chem 271:15436–15442[Abstract/Free Full Text]
  28. Sasano H, Fukushima K, Sasaki I, Matsuno S, Nagura H, Krozowski ZS 1992 Immunolocalization of mineralocorticoid receptor in human kidney, pancreas, salivary, mammary and sweat glands: a light and electron microscopic immunohistochemical study. J Endocrinol 132:305–310[Abstract/Free Full Text]
  29. Farman N, Oblin ME, Lombes M, Delahaye F, Westphal HM, Bonvalet JP, Gasc JM 1991 Immunolocalization of gluco- and mineralocorticoid receptors in rabbit kidney. Am J Physiol 260:C226–C233
  30. Condon J, Gosden C, Gardener D, Nickson P, Hewison M, Howie AJ, Stewart PM 1998 Expression of type 2 11ß-hydroxysteroid dehydrogenase and corticosteroid hormone receptors in early human fetal life. J Clin Endocrinol Metab 83:4490–4497[Abstract/Free Full Text]
  31. Li KX, Obeyesekere VR, Krozowski ZS, Ferrari P 1997 Oxoreductase and dehydrogenase activities of the human and rat 11ß-hydroxysteroid dehydrogenase type 2 enzyme. Endocrinology 138:2948–5292[Abstract/Free Full Text]
  32. Li KX, Smith RE, Ferrari P, Funder JW, Krozowski ZS 1996 Rat 11ß-hydroxysteroid dehydrogenase type 2 enzyme is expressed at low levels in the placenta and is modulated by adrenal steroids in the kidney. Mol Cell Endocrinol 120:67–75[CrossRef][Medline]



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Y. Sekine, Y. Nishibori, Y. Akimoto, A. Kudo, N. Ito, D. Fukuhara, R. Kurayama, E. Higashihara, E. Babu, Y. Kanai, et al.
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[Abstract] [Full Text] [PDF]

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 J. Am. Soc. Nephrol.Home page
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[Full Text] [PDF]

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[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
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