|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 52, 49142-49147, December 28, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Mesangial expansion is a key feature
in the pathogenesis of numerous renal diseases involving the
glomerulus. Studies indicate that mutations in apolipoprotein E (apoE)
might independently contribute to kidney dysfunction. Although the role
of apoE as an atheroprotective molecule is well established, its role
in kidney is unclear. In this study, we sought to explore whether apoE
has a protective function in kidney. Northern blotting and reverse
transcriptase-polymerase chain reaction showed apoE expression in
kidney, and mesangial cell is a major source of apoE in kidney. In the
kidneys of 14-16-month-old apoE-null mice, hematoxylin-eosin (HE)
staining revealed increased mesangial cell proliferation and matrix
formation compared with wild type mice or apoB-overexpressing mice,
which have elevated plasma cholesterol and triglycerides. These data
suggest that lack of apoE, rather than hyperlipidemia, contributes to
increased mesangial expansion. We isolated mesangial cells from mouse
kidney and determined the effect of apoE on cell growth. ApoE (E3, 10 µg/ml) completely inhibited serum, platelet-derived growth factor (10 ng/ml), as well as low density lipoprotein-induced mesangial cell
proliferation. Among the three isoforms, E3 was found to be most
effective in inhibiting mesangial cell proliferation. ApoE did not show
any cytotoxic effect, and moreover, inhibited mesangial cell apoptosis
induced by oxidized low density lipoprotein. These data suggest that
apoE regulates growth as well as survival of mesangial cells. We
previously showed that apoE induces matrix heparan sulfate proteoglycan
(HSPG) in vascular cells, which has an antiproliferative effect.
Similarly, apoE induced the mesangial matrix HSPG. Perlecan is the
major HSPG of mesangial matrix and subendothelial space, and consistent
with this, blockade of perlecan reversed the antiproliferative effect
of apoE. Immunohistochemistry revealed reduced staining of
perlecan in kidney from apoE-null mice. Because the loss of anionic
HSPG in the basement membrane and mesangial matrix is associated with
disruption of filtration barrier, these data suggest a novel role for
kidney apoE in preserving the filtration barrier. In summary, apoE has
a protective function in kidney as an autocrine regulator of
mesangial expansion and kidney function.
A Protective Role for Kidney Apolipoprotein E
REGULATION OF MESANGIAL CELL PROLIFERATION AND MATRIX
EXPANSION*
,,, and
**
Department of Radiation Oncology
and ¶ Medicine, North Shore-Long Island Jewish Health System,
Manhasset, New York 11030, the § Division of Preventive
Medicine, Department of Medicine, Columbia University, New York,
New York 10032, and the Reddy US Therapeutics,
Norcross, Georgia 30071
*
This work was supported in part by grants from the American
Heart Association (Heritage affiliate).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Guan, H.-L. Zhao, L. Baum, Y. Sui, L. He, H. Wong, F. M. M. Lai, P. C. Y. Tong, and J. C. N. Chan Apolipoprotein E polymorphism and expression in type 2 diabetic patients with nephropathy: clinicopathological correlation Nephrol. Dial. Transplant., June 1, 2009; 24(6): 1889 - 1895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Doorenbos, S.-W. Tsaih, S. Sheehan, N. Ishimori, G. Navis, G. Churchill, K. DiPetrillo, and R. Korstanje Quantitative Trait Loci for Urinary Albumin in Crosses Between C57BL/6J and A/J Inbred Mice in the Presence and Absence of Apoe Genetics, May 1, 2008; 179(1): 693 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kinomura, H. Sugiyama, T. Saito, A. Matsunaga, K.-e. Sada, M. Kanzaki, Y. Takazawa, Y. Maeshima, H. Yanai, and H. Makino A novel variant apolipoprotein E Okayama in a patient with lipoprotein glomerulopathy Nephrol. Dial. Transplant., February 1, 2008; 23(2): 751 - 756. [Full Text] [PDF]
|
|
|
|
 |
|
 F. Michel, S. Simonet, C. Vayssettes-Courchay, F. Bertin, P. Sansilvestri-Morel, F. Bernhardt, J. Paysant, J.-S. Silvestre, B. I. Levy, M. Feletou, et al. Altered TP receptor function in isolated, perfused kidneys of nondiabetic and diabetic ApoE-deficient mice Am J Physiol Renal Physiol, January 1, 2008; 294(1): F120 - F129. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Hsu, W. H. L. Kao, J. Coresh, J. S. Pankow, J. Marsh-Manzi, E. Boerwinkle, and M. S. Bray Apolipoprotein E and Progression of Chronic Kidney Disease JAMA, June 15, 2005; 293(23): 2892 - 2899. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sultmann, A. v. Heydebreck, W. Huber, R. Kuner, A. Buness, M. Vogt, B. Gunawan, M. Vingron, L. Fuzesi, and A. Poustka Gene Expression in Kidney Cancer Is Associated with Cytogenetic Abnormalities, Metastasis Formation, and Patient Survival Clin. Cancer Res., January 15, 2005; 11(2): 646 - 655. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-C. Chen, G. Pohl, T.-L. Wang, P. J. Morin, B. Risberg, G. B. Kristensen, A. Yu, B. Davidson, and I.-M. Shih Apolipoprotein E Is Required for Cell Proliferation and Survival in Ovarian Cancer Cancer Res., January 1, 2005; 65(1): 331 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Yue, N. Rasouli, G. Ranganathan, P. A. Kern, and T. Mazzone Divergent Effects of Peroxisome Proliferator-activated Receptor {gamma} Agonists and Tumor Necrosis Factor {alpha} on Adipocyte ApoE Expression J. Biol. Chem., November 12, 2004; 279(46): 47626 - 47632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. N. Liberopoulos, G. A. Miltiadous, M. Cariolou, R. Kalaitzidis, K. C. Siamopoulos, and M. S. Elisaf Influence of apolipoprotein E polymorphisms on serum creatinine levels and predicted glomerular filtration rate in healthy subjects Nephrol. Dial. Transplant., August 1, 2004; 19(8): 2006 - 2012. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Lassila, K. K. Seah, T. J. Allen, V. Thallas, M. C. Thomas, R. Candido, W. C. Burns, J. M. Forbes, A. C. Calkin, M. E. Cooper, et al. Accelerated Nephropathy in Diabetic Apolipoprotein E-Knockout Mouse: Role of Advanced Glycation End Products J. Am. Soc. Nephrol., August 1, 2004; 15(8): 2125 - 2138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Vitt, D. Gietzen, K. Stevens, J. Wingrove, S. Becha, S. Bulloch, J. Burrill, N. Chawla, J. Chien, M. Crawford, et al. Identification of Candidate Disease Genes by EST Alignments, Synteny, and Expression and Verification of Ensembl Genes on Rat Chromosome 1q43-54 Genome Res., April 1, 2004; 14(4): 640 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-i. Araki, D. Koya, T. Makiishi, T. Sugimoto, M. Isono, R. Kikkawa, A. Kashiwagi, and M. Haneda APOE Polymorphism and the Progression of Diabetic Nephropathy in Japanese Subjects With Type 2 Diabetes: Results of a prospective observational follow-up study Diabetes Care, August 1, 2003; 26(8): 2416 - 2420. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |