Cellular basis of diabetic nephropathy: V. Endoglin expression levels and diabetic nephropathy risk in patients with Type 1 diabetes

Alvarez-Muñoz, Patricia; Mauer, Michael; Kim, Youngki; Rich, Stephen S.; Miller, Michael E.; Russell, Gregory B.; Lopez-Novoa, José M.; Caramori, M. Luiza

doi:10.1016/j.jdiacomp.2009.03.004

« Previous Next »Journal of Diabetes and Its Complications
Volume 24, Issue 4 , Pages 242-249, July 2010

Cellular basis of diabetic nephropathy: V. Endoglin expression levels and diabetic nephropathy risk in patients with Type 1 diabetes

Patricia Alvarez-Muñoz
- Department of Physiology and Pharmacology, University of Salamanca, Spain
Michael Mauer
- Department of Medicine, University of Minnesota, MN, USA
- Department of Pediatrics, University of Minnesota, MN, USA
Youngki Kim
- Department of Pediatrics, University of Minnesota, MN, USA
Stephen S. Rich
- Department of Public Health Sciences, University of Virginia, VA, USA
Michael E. Miller
- Department of Biostatistical Sciences, Wake Forest University School of Medicine, NC, USA
Gregory B. Russell
- Department of Biostatistical Sciences, Wake Forest University School of Medicine, NC, USA
José M. Lopez-Novoa
- Department of Physiology and Pharmacology, University of Salamanca, Spain
M. Luiza Caramori
- Department of Medicine, University of Minnesota, MN, USA
- Department of Pediatrics, University of Minnesota, MN, USA
- Corresponding author. Tel.: +1 612 624 5150; fax: +1 612 626 3133.

Received 17 June 2008; received in revised form 5 February 2009; accepted 20 March 2009. published online 24 April 2009.

Abstract

Endoglin is an accessory receptor molecule that, in association with transforming growth factor β (TGF-β) family receptors Types I and II, binds TGF-β1, TGF-β3, activin A, bone morphogenetic protein (BMP)-2 and BMP-7, regulating TGF-β dependent cellular responses. Relevant to diabetic nephropathy, endoglin, expressed in vascular endothelial and smooth muscle cells, fibroblasts, and mesangial cells, negatively regulates extracellular matrix (ECM). The aim of this study was to evaluate endoglin expression in cultured skin fibroblasts from patients with Type 1 diabetes with and without diabetic nephropathy. Kidney and skin biopsies were performed in 125 Type 1 diabetic patients. The 20 with the fastest rate of mesangial expansion (estimated by electron microscopy) and proteinuria (“fast-track”) and the 20 with the slowest rate and normoalbuminuria (“slow-track”), along with 20 controls were studied. Endoglin mRNA expression was assessed by microarray and quantitative real-time polymerase chain reaction (QRT-PCR) and protein expression by Western blot. Age and sex distribution were similar among groups. Diabetes duration was similar (20±8 vs. 24±7 years), hemoglobin A1c lower (8.4±1.2% vs. 9.4±1.5%), and glomerular filtration rate higher (115±13 vs. 72±20 ml/min per 1.73 m²) in slow-track vs. fast-track patients. Microarray endoglin mRNA expression levels were higher in slow-track (1516.0±349.9) than fast-track (1211.0±274.9; P=.008) patients or controls (1223.1±422.9; P=.018). This was confirmed by QRT-PCR. Endoglin protein expression levels correlated with microarray (r=0.59; P=.044) and QRT-PCR (r=0.61; P=.034) endoglin mRNA expression. These studies are compatible with the hypothesis that slow-track Type 1 diabetic patients, strongly protected from diabetic nephropathy, have distinct cellular behaviors that may be associated with reduced ECM production.

Keywords: Diabetic nephropathy, Type 1 diabetes, Endoglin