The MIF Receptor CD74 in Diabetic Podocyte Injury

被引：102

作者：

Dolores Sanchez-Nino, Maria ^{[1
]}

Belen Sanz, Ana ^{[1
]}

Ihalmo, Pekka ^{[2
,3
]}

Lassila, Markus ^{[4
]}

Holthofer, Harry ^{[5
]}

Mezzano, Sergio ^{[6
]}

Aros, Claudio ^{[6
]}

Groop, Per-Henrik ^{[2
,3
]}

Saleem, Moin A. ^{[7
]}

Mathieson, Peter W. ^{[7
]}

Langham, Robert ^{[8
]}

Kretzler, Matthias ^{[9
]}

Nair, Viji ^{[9
]}

Lemley, Kevin V. ^{[10
]}

Nelson, Robert G. ^{[11
]}

Mervaala, Eero ^{[12
]}

Mattinzoli, Deborah ^{[13
]}

Rastaldi, Maria Pia ^{[13
]}

Ruiz-Ortega, Marta ^{[1
]}

Luis Martin-Ventura, Jose ^{[1
]}

Egido, Jesus ^{[1
]}

Ortiz, Alberto ^{[1
]}

机构：

[1] Univ Autonoma Madrid, Fdn Jimenez Diaz, Fdn Renal Inigo Alvarez de Toledo, Madrid 28040, Spain

[2] Univ Helsinki, Folkhalsan Res Ctr, Folkhalsan Inst Genet, Helsinki, Finland

[3] Univ Helsinki, Cent Hosp, Dept Med, Div Nephrol, Helsinki, Finland

[4] Univ Helsinki, Haartman Inst, Dept Bacteriol & Immunol, FIN-00014 Helsinki, Finland

[5] Dublin City Univ, Ctr Bioanalyt Sci, Dublin 9, Ireland

[6] Univ Austral Chile, Div Nephrol, Valdivia, Chile

[7] Univ Bristol, Acad & Childrens Renal Unit, Bristol, Avon, England

[8] Univ Melbourne, St Vincents Hosp, Dept Med, Melbourne, Vic 3010, Australia

[9] Univ Michigan, Div Nephrol, Ann Arbor, MI 48109 USA

[10] Childrens Hosp Los Angeles, Div Nephrol, Los Angeles, CA 90027 USA

[11] NIDDK, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA

[12] Univ Helsinki, Inst Biomed Pharmacol, FIN-00014 Helsinki, Finland

[13] Fdn DAmico Ric Malattie Renali, Milan, Italy

来源：

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2009年 / 20卷 / 02期

关键词：

MIGRATION INHIBITORY FACTOR; TUBULAR EPITHELIAL-CELLS; RENAL INJURY; P38; EXPRESSION; APOPTOSIS; KINASE; NEPHROPATHY; ACTIVATION; INDUCTION;

D O I：

10.1681/ASN.2008020194

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Although metabolic derangement plays a central role in diabetic nephropathy, a better understanding of secondary mediators of injury may lead to new therapeutic strategies. Expression of macrophage migration inhibitory factor (MIF) is increased in experimental diabetic nephropathy, and increased tubulointerstitial mRNA expression of its receptor, CD74, has been observed in human diabetic nephropathy. Whether CD74 transduces MIF signals in podocytes, however, is unknown. Here, we found glomerular and tubulointerstitial CD74 mRNA expression to be increased in Pima Indians with type 2 diabetes and diabetic nephropathy. Immunohistochemistry confirmed the increased glomerular and tubular expression of CD74 in clinical and experimental diabetic nephropathy and localized glomerular CD74 to podocytes. In cultured human podocytes, CD74 was expressed at the cell surface, was upregulated by high concentrations of glucose and TNF-alpha, and was activated by MIF, leading to phosphorylation of extracellular signal-regulated kinase 1/2 and p38. High glucose also induced CD74 expression in a human proximal tubule cell line (HK2). In addition, MIF induced the expression of the inflammatory mediators TRAIL and monocyte chemoattractant protein 1 in podocytes and HK2 cells in a p38-dependent manner. These data suggest that CD74 acts as a receptor for MIF in podocytes and may play a role in the pathogenesis of diabetic nephropathy.

引用

页码：353 / 362

页数：10

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