Epidermal growth factor receptor promotes glomerular injury and renal failure in rapidly progressive crescentic glomerulonephritis

被引：191

作者：

Bollee, Guillaume ^{[1
,2
]}

Flamant, Martin ^{[3
,4
]}

Schordan, Sandra ^{[5
]}

Fligny, Cecile ^{[1
,2
]}

Rumpel, Elisabeth ^{[5
]}

Milon, Marine ^{[1
,2
]}

Schordan, Eric ^{[5
]}

Sabaa, Nathalie ^{[3
,4
]}

Vandermeersch, Sophie ^{[6
,7
]}

Galaup, Ariane ^{[8
,9
]}

Rodenas, Anita ^{[10
]}

Casal, Ibrahim ^{[11
,12
]}

Sunnarborg, Susan W. ^{[13
]}

Salant, David J. ^{[14
]}

Kopp, Jeffrey B. ^{[15
]}

Threadgill, David W. ^{[16
]}

Quaggin, Susan E. ^{[17
]}

Dussaule, Jean-Claude ^{[6
,7
,18
]}

Germain, Stephane ^{[8
,9
]}

Mesnard, Laurent ^{[6
,7
]}

Endlich, Karlhans ^{[5
]}

Boucheix, Claude ^{[11
,12
]}

Belenfant, Xavier ^{[19
]}

Callard, Patrice ^{[7
,10
]}

Endlich, Nicole ^{[5
]}

Tharaux, Pierre-Louis ^{[1
,2
,20
]}

机构：

[1] INSERM, Unite Mixte Rech UMR 970, Paris Cardiovasc Res Ctr, Paris, France

[2] Univ Paris 05, Paris, France

[3] Univ Paris Diderot, Paris, France

[4] Hop Bichat Claude Bernard, AP HP, Serv Physiol Explorat Fonct, F-75877 Paris, France

[5] Univ Med Greifswald, Inst Anat & Zellbiol, Greifswald, Germany

[6] Hop Tenon, INSERM, UMR702, F-75970 Paris, France

[7] Sorbonne Univ, Univ Paris 06, Paris, France

[8] INSERM, Ctr Interdisciplinary Res Biol, Ctr Natl Rech Sci, UMR 7241,U1050, Paris, France

[9] Coll France, Chaire Med Expt, F-75231 Paris, France

[10] Hop Tenon, AP HP, Serv Anat & Cytol Pathol, F-75970 Paris, France

[11] Hop Paul Brousse, INSERM, UMR 1004, Inst Andre Lwoff, Villejuif, France

[12] Univ Paris 11, Villejuif, France

[13] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC USA

[14] Boston Univ, Med Ctr, Renal Sect, Boston, MA USA

[15] NIDDK, Kidney Dis Sect, Bethesda, MD USA

[16] N Carolina State Univ, Dept Genet, Raleigh, NC 27695 USA

[17] Univ Toronto, Mt Sinai Hosp, St Michaels Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[18] Hop St Antoine, AP HP, Serv Physiol Explorat Fonct, F-75571 Paris, France

[19] Ctr Hosp Intercommunal Andre Gregoire, Serv Nephrol & Dialyse, Montreuil, France

[20] Hop Europeen Georges Pompidou, Assistance Publ Hop Paris, Serv Nephrol, Paris, France

来源：

NATURE MEDICINE | 2011年 / 17卷 / 10期

基金：

美国国家卫生研究院;

关键词：

PARIETAL EPITHELIAL-CELLS; GENE-EXPRESSION; CELLULAR CRESCENTS; ENDOTHELIAL-CELLS; NEPHROTOXIC SERUM; MEDIATED-IMMUNITY; BOWMANS CAPSULE; TRANSGENIC MICE; MESANGIAL CELLS; T-LYMPHOCYTES;

D O I：

10.1038/nm.2491

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Rapidly progressive glomerulonephritis (RPGN) is a life-threatening clinical syndrome and a morphological manifestation of severe glomerular injury that is marked by a proliferative histological pattern ('crescents') with accumulation of T cells and macrophages and proliferation of intrinsic glomerular cells. We show de novo induction of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in intrinsic glomerular epithelial cells (podocytes) from both mice and humans with RPGN. HB-EGF induction increases phosphorylation of the epidermal growth factor receptor (EGFR, also known as ErbB1) in mice with RPGN. In HB-EGF-deficient mice, EGFR activation in glomeruli is absent and the course of RPGN is improved. Autocrine HB-EGF induces a phenotypic switch in podocytes in vitro. Conditional deletion of the Egfr gene from podocytes of mice alleviates the severity of RPGN. Likewise, pharmacological blockade of EGFR also improves the course of RPGN, even when started 4 d after the induction of experimental RPGN. This suggests that targeting the HB-EGF-EGFR pathway could also be beneficial in treatment of human RPGN.

引用

页码：1242 / U272

页数：10

共 57 条

[1]

Inhibition of the epidermal growth factor receptor preserves podocytes and attenuates albuminuria in experimental diabetic nephropathy [J].