Human immunodeficiency virus downregulates podocyte apoE expression

被引：14

作者：

Arora, Shitij ^{[1
]}

Husain, Mohammad ^{[1
]}

Kumar, Dileep ^{[1
]}

Patni, Hitesh ^{[1
]}

Pathak, Shresh ^{[1
]}

Mehrotra, Devi ^{[1
]}

Reddy, Vivek Kathi ^{[1
]}

Reddy, Lalit Rajeev ^{[1
]}

Salhan, Divya ^{[1
]}

Yadav, Anju ^{[1
]}

Mathieson, Peter W. ^{[2
]}

Saleem, Moin A. ^{[2
]}

Chander, Praveen N. ^{[3
]}

Singhal, Pravin C. ^{[1
]}

机构：

[1] N Shore Long Isl Jewish Med Ctr, Feinstein Inst Med Res, Ctr Immunol, Manhasset, NY USA

[2] Univ Bristol, Childrens Renal Unit, Bristol, Avon, England

[3] New York Med Coll, Dept Pathol, Valhalla, NY 10595 USA

来源：

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY | 2009年 / 297卷 / 03期

基金：

英国医学研究理事会;

关键词：

apolipoprotein E; pelecan; mesangial cells; HEPARAN-SULFATE PROTEOGLYCANS; APOLIPOPROTEIN-A-I; CHOLESTEROL TRANSPORT; ALZHEIMERS-DISEASE; METABOLIC SYNDROME; PEPTIDE ANALOGS; TRANSGENIC MICE; LIPID RAFTS; VIRAL ENTRY; HIV-1;

D O I：

10.1152/ajprenal.90668.2008

中图分类号：

Q4 [生理学];

学科分类号：

071003 ;

摘要：

Arora S, Husain M, Kumar D, Patni H, Pathak S, Mehrotra D, Reddy VK, Reddy LR, Salhan D, Yadav A, Mathieson PW, Saleem MA, Chander PN, Singhal PC. Human immunodeficiency virus downregulates podocyte apoE expression. Am J Physiol Renal Physiol 297: F653-F661, 2009. First published June 24, 2009; doi:10.1152/ajprenal.90668.2008.-Apolipoprotein E (apoE) has been demonstrated to play an important role in providing protection against mesangial cell injury. In the present study, we evaluated the role of apoE and its associated downstream effects in human immunodeficiency virus (HIV)-associated nephropathy (HIVAN). Control (n = 6) and age-and sex-matched HIV-1 transgenic mice (Tg26, n = 6) were evaluated for their renal cortical expression of apoE. Renal tissue from Tg26 mice not only showed decreased apoE expression but also displayed downregulation of perlecan mRNA expression. In in vitro studies, conditionally immortalized human podocytes (CIHPs) were transduced with either NL4-3HIV (an HIV-1 construct lacking gag and pol, used for the development of Tg26 mouse model; NL4-3/CIHP) or empty vector (EV/CIHP); NL4-3/CIHPs and EV/CIHPs were studied for apoE mRNA expression. NL4-3/CIHPs showed reduction in apoE expression compared with EV/CIHPs. To evaluate the role of HIV-1 genes in the modulation of apoE expression, conditionally immortalized mouse podocytes (CIMPs) were transduced with individual HIV-1 gene constructs. Only nef-transduced CIMPs showed a decrease in apoE expression. To confirm this effect of nef in CIHPs, microarray analysis was performed in stable colonies of nef/CIHPs and EV/CIHPs. nef/CIHPs showed a 60% decrease in apoE and a 90% reduction in heparan sulfate mRNA expression. Moreover, nef transgenic mice showed a decrease in renal tissue expression of both apoE and perlecan. Both Tg26 and nef transgenic mice also showed areas of mesangial cell proliferation. These findings suggest that HIV-1-induced reduction in podocyte apoE expression and associated downregulation of podocyte perlecan might be contributing to mesangial cell (MC) phenotype in HIVAN.

引用

页码：F653 / F661

页数：9

共 47 条

[1]

BOURGOIGNIE JJ, 1991, KIDNEY INT, V40, pS19

[2] HIV entry inhibitors: mechanisms of action and resistance pathways [J].

Briz, V ;

Poveda, E ;

Soriano, V .

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2006, 57 (04) :619-627

[3] Mesangial expansion associated with glomerular endothelial cell activation and macrophage recruitment is developing in hyperlipidaemic apoE null mice [J].

Bruneval, P ;

Bariéty, J ;

Lair, MF ;

Mandet, C ;

Heudes, D ;

Nicoletti, A .

NEPHROLOGY DIALYSIS TRANSPLANTATION, 2002, 17 (12) :2099-2107

[4] Apolipoprotein (apo) E4 enhances HIV-1 cell entry in vitro, and the APOE ε4/ε4 genotype accelerates HIV disease progression [J].

Burt, Trevor D. ;

Agan, Brian K. ;

Marconi, Vincent C. ;

He, Weijing ;

Kulkarni, Hemant ;

Mold, Jeffrey E. ;

Cavrois, Marielle ;

Huang, Yadong ;

Mahley, Robert W. ;

Dolan, Matthew J. ;

McCune, Joseph M. ;

Ahuja, Sunil K. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (25) :8718-8723

[5] Lipid rafts and HIV-1: from viral entry to assembly of progeny virions [J].

Campbell, SM ;

Crowe, SM ;

Mak, J .

JOURNAL OF CLINICAL VIROLOGY, 2001, 22 (03) :217-227

[6] A protective role for kidney apolipoprotein E - Regulation of mesangial cell proliferation and matrix expansion [J].

Chen, GP ;

Paka, L ;

Kako, Y ;

Singhal, P ;

Duan, WL ;

Pillarisetti, S .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (52) :49142-49147

[7] Potential role for heparan sulfate proteoglycans in regulation of transforming growth factor-β(TGF-β) by modulating assembly of latent TGF-β-binding protein-1 [J].

Chen, Qian ;

Sivakumar, Pitchumani ;

Barley, Craig ;

Peters, Donna M. ;

Gomes, Ronald R. ;

Farach-Carson, Mary C. ;

Dallas, Sarah L. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (36) :26418-26430

[8] Proteomic and biochemical analysis of purified human immunodeficiency virus type 1 produced from infected monocyte-derived macrophages [J].

Chertova, Elena ;

Chertov, Oleg ;

Coren, Lori V. ;

Roser, James D. ;

Trubey, Charles M. ;

Bess, Julian W., Jr. ;

Sowder, Raymond C., II ;

Barsov, Eugene ;

Hood, Brian L. ;

Fisher, Robert J. ;

Nagashima, Kunio ;

Conrads, Thomas P. ;

Veenstra, Timothy D. ;

Lifson, Jeffrey D. ;

Ott, David E. .

JOURNAL OF VIROLOGY, 2006, 80 (18) :9039-9052

[9] Heparan sulfate proteoglycans in experimental models of diabetes: a role for perlecan in diabetes complications [J].

Conde-Knape, K .

DIABETES-METABOLISM RESEARCH AND REVIEWS, 2001, 17 (06) :412-421

[10] GENE DOSE OF APOLIPOPROTEIN-E TYPE-4 ALLELE AND THE RISK OF ALZHEIMERS-DISEASE IN LATE-ONSET FAMILIES [J].

CORDER, EH ;

SAUNDERS, AM ;

STRITTMATTER, WJ ;

SCHMECHEL, DE ;

GASKELL, PC ;

SMALL, GW ;

ROSES, AD ;

HAINES, JL ;

PERICAKVANCE, MA .

SCIENCE, 1993, 261 (5123) :921-923

← 1 2 3 4 5 →