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

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

doi:10.1016/j.jdiacomp.2009.03.004

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

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

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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.

Original language	English (US)
Pages (from-to)	242-249
Number of pages	8
Journal	Journal of Diabetes and its Complications
Volume	24
Issue number	4
DOIs	https://doi.org/10.1016/j.jdiacomp.2009.03.004
State	Published - Jul 2010

Bibliographical note

Funding Information:
Patricia Alvarez-Muñoz is a fellow from the Ministerio de Educación y Ciencia, Spain. Dr. M. Luiza Caramori was previously supported by a Research Fellowship grant from the Juvenile Diabetes Research Foundation International (JDRFI) and is currently a JDRFI Career Development Award recipient. This work was supported by grants from the National Institutes of Health (DK13083, DK54638 and DK070210), National Center for Research Resources (M01-RR00400), Spanish Ministerio de Ciencia y Tecnología (BFU2004-00285/BFI) and Instituto de Salud Carlos III (ISCIII-RETIC RD/0016/0002). We thank Dr. Francisco Sanchez-Madrid for the gift of TEA 1/58 antibody. We thank Messrs. John Basgen and Thomas Groppoli for performing the morphometric studies and Ms. Kim Pinkham and Mr. Paul Walker for assisting with the cellular studies.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Diabetic nephropathy
Endoglin
Type 1 diabetes

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10.1016/j.jdiacomp.2009.03.004

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@article{dc4b7e7475bf4b369f58c3eea2be7a06,

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

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, Endoglin, Type 1 diabetes",

author = "Patricia Alvarez-Mu{\~n}oz and Michael Mauer and Youngki Kim and Rich, \{Stephen S.\} and Miller, \{Michael E.\} and Russell, \{Gregory B.\} and Lopez-Novoa, \{Jos{\'e} M.\} and Caramori, \{M. Luiza\}",

note = "Funding Information: Patricia Alvarez-Mu{\~n}oz is a fellow from the Ministerio de Educaci{\'o}n y Ciencia, Spain. Dr. M. Luiza Caramori was previously supported by a Research Fellowship grant from the Juvenile Diabetes Research Foundation International (JDRFI) and is currently a JDRFI Career Development Award recipient. This work was supported by grants from the National Institutes of Health (DK13083, DK54638 and DK070210), National Center for Research Resources (M01-RR00400), Spanish Ministerio de Ciencia y Tecnolog{\'i}a (BFU2004-00285/BFI) and Instituto de Salud Carlos III (ISCIII-RETIC RD/0016/0002). We thank Dr. Francisco Sanchez-Madrid for the gift of TEA 1/58 antibody. We thank Messrs. John Basgen and Thomas Groppoli for performing the morphometric studies and Ms. Kim Pinkham and Mr. Paul Walker for assisting with the cellular studies.",

year = "2010",

month = jul,

doi = "10.1016/j.jdiacomp.2009.03.004",

language = "English (US)",

volume = "24",

pages = "242--249",

journal = "Journal of Diabetes and its Complications",

issn = "1056-8727",

publisher = "Elsevier Inc.",

number = "4",

}

TY - JOUR

T1 - Cellular basis of diabetic nephropathy

T2 - V. Endoglin expression levels and diabetic nephropathy risk in patients with Type 1 diabetes

AU - Alvarez-Muñoz, Patricia

AU - Mauer, Michael

AU - Kim, Youngki

AU - Rich, Stephen S.

AU - Miller, Michael E.

AU - Russell, Gregory B.

AU - Lopez-Novoa, José M.

AU - Caramori, M. Luiza

N1 - Funding Information: Patricia Alvarez-Muñoz is a fellow from the Ministerio de Educación y Ciencia, Spain. Dr. M. Luiza Caramori was previously supported by a Research Fellowship grant from the Juvenile Diabetes Research Foundation International (JDRFI) and is currently a JDRFI Career Development Award recipient. This work was supported by grants from the National Institutes of Health (DK13083, DK54638 and DK070210), National Center for Research Resources (M01-RR00400), Spanish Ministerio de Ciencia y Tecnología (BFU2004-00285/BFI) and Instituto de Salud Carlos III (ISCIII-RETIC RD/0016/0002). We thank Dr. Francisco Sanchez-Madrid for the gift of TEA 1/58 antibody. We thank Messrs. John Basgen and Thomas Groppoli for performing the morphometric studies and Ms. Kim Pinkham and Mr. Paul Walker for assisting with the cellular studies.

PY - 2010/7

Y1 - 2010/7

N2 - 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.

AB - 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.

KW - Diabetic nephropathy

KW - Endoglin

KW - Type 1 diabetes

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UR - https://www.scopus.com/pages/publications/77953024536#tab=citedBy

U2 - 10.1016/j.jdiacomp.2009.03.004

DO - 10.1016/j.jdiacomp.2009.03.004

M3 - Article

C2 - 19395281

AN - SCOPUS:77953024536

SN - 1056-8727

VL - 24

SP - 242

EP - 249

JO - Journal of Diabetes and its Complications

JF - Journal of Diabetes and its Complications

IS - 4

ER -

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

Abstract

Bibliographical note

UN SDGs

Keywords

Publisher link

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