No conflicts of interest were declared.
Podocyte loss involves MDM2-driven mitotic catastrophe
Version of Record online: 7 JUN 2013
Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 230, Issue 3, pages 322–335, July 2013
How to Cite
Mulay, S. R., Thomasova, D., Ryu, M., Kulkarni, O. P., Migliorini, A., Bruns, H., Gröbmayr, R., Lazzeri, E., Lasagni, L., Liapis, H., Romagnani, P. and Anders, H.-J. (2013), Podocyte loss involves MDM2-driven mitotic catastrophe. J. Pathol., 230: 322–335. doi: 10.1002/path.4193
- Issue online: 7 JUN 2013
- Version of Record online: 7 JUN 2013
- Manuscript Accepted: 18 MAR 2013
- Manuscript Revised: 21 FEB 2013
- Manuscript Received: 3 DEC 2012
|path4193-sup-0001-FigureS1.tif||TIFF image||10251K||MDM2 expression in the glomerulus throughout the course of AN. MDM2 immunostaining (red) was assessed by confocal microscopy. In glomeruli the expression mostly co-localized with nephrin (green) which mark podocytes. Original magnification 400×.|
|path4193-sup-0002-FigureS2.tif||TIFF image||18562K||MDM2 expression in the tubular compartment throughout the course of AN. In the tubulointerstitial compartment MDM2 staining (red) localized to lectin-positive proximal tubules (green) as well as to lectin-negative distal tubules. Original magnification 200×.|
|path4193-sup-0003-FigureS3.tif||TIFF image||2686K||TNF immunostaining. Kidneys of Balb/c mice 2 weeks after adriamycin injection were stained for TNF-α. Representative images are shown at a magnification of 400×. Note TNF signal in podocytes, which is lacking in nutlin-3a-treated mice.|
|path4193-sup-0004-FigureS4.tif||TIFF image||17907K||Semi-quantitative assessment of glomerular lesions. A: PAS-stained renal sections were used to quantify normal glomeruli with no lesions, glomeruli with segmental lesions, and globally sclerosed glomeruli for which representative images are shown. Original magnification 400×. B: Using these criteria, Balb/c mice with AN displayed a progressive decrease in the numbers of glomeruli with no lesions in favour of progressively increasing numbers of glomeruli with global lesions. Treatment with nutlin-3a from week 2 to week 4 had no significant effect on these measures. Data are means ± SEM for each time point.|
|path4193-sup-0005-FigureS5.tif||TIFF image||1245K||MDM2 blockade and proliferation of kidney cells. Renal sections from vehicle- and nutlin-3a- treated kidneys were stained for Ki-67, a cell proliferation marker as described in methods. A: Quantitative assessment of the numbers of proliferating glomerular cells from vehicle- and nutlin-3a-treated kidneys at respective time points, from week 1 to week 2 (left graph) and from week 2 to week 4 (right graph). B: Quantitative assessment of proliferating tubular cells from vehicle- and nutlin-3a-treated kidneys at respective time points, from week 1 to week 2 (left graph) and from week 2 to week 4 (right graph). Data are means ± SEM.|
|path4193-sup-0006-FigureS6.tif||TIFF image||12921K||MDM2 blockade and tubulointerstitial inflammation in AN. A: Total mRNA was prepared from vehicle- and nutlin-3a-treated kidneys. The mRNA expression levels were determined for the indicated cytokines and chemokines by real-time PCR and expressed as mean of the ratio versus the respective 18s rRNA level ± SEM. p values for the comparison of nutlin-3a- versus vehicle treatment are as indicated. B: Renal sections from vehicle- and nutlin-3a-treated kidneys at week 4 were stained for different leukocyte markers as described in methods. F4/80-positive macrophages were quantified by digital morphometry and data are expressed as percentage of hpf. CD3+ T cells were counted per hpf. Data are means ± SEM of 25 hpf per kidney per group. *p < 0.05 nutlin-3a versus vehicle-treated mice at week 4.|
|path4193-sup-0007-FigureS7.tif||TIFF image||11325K||MDM2 blockade and interstitial fibrosis. A: Representative images of kidneys at week 4 from α-SMA stains of vehicle- and nutlin-3a-treated groups are shown at a magnification of 200×. B: α-SMA positive area was quantified by digital morphometry and data are expressed as percentage of hpf. C: Total mRNA was prepared from vehicle- and nutlin-3a-treated kidneys. The target mRNA expression levels were determined by real-time PCR and expressed as mean of the ratio versus the respective 18s rRNA level ± SEM. Data are means ± SEM. *p < 0.05 nutlin-3a- versus vehicle-treated mice at week 4.|
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