Glomerular expression of neuronal activity-regulated pentraxin precedes the development of anti-Thy-1-induced progressive glomerulosclerosis

J. A. Aben; D. H. Ijpelaar; H. Baelde; P. Worley; N. Noble; J. A. Bruijn; E. De Heer

doi:10.1038/sj.ki.5001757

Glomerular expression of neuronal activity-regulated pentraxin precedes the development of anti-Thy-1-induced progressive glomerulosclerosis

J. A. Aben, D. H. Ijpelaar, H. Baelde, P. Worley, N. Noble, J. A. Bruijn, E. De Heer

School of Medicine

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

3 Scopus citations

Abstract

Although it is clear that genetic predispositions play a role in progressive glomerulosclerosis, identification of specific genes is difficult because of natural genetic heterogeneity among individuals. We have reported a differential susceptibility to progressive glomerulosclerosis after induction of experimental glomerulonephritis anti-Thy-1 nephritis in Lewis rat substrains. Glomerular lesions in Lewis/Møllegard rats resolve spontaneously, whereas Lewis/Maastricht (Lew/Maa) rats develop progressive glomerulosclerosis. This predisposition for progressive glomerulosclerosis is governed by unknown genes that are expressed by renal cells. Here, differential gene expression analysis using a rat complementary DNA micro array revealed neuronal activity-regulated pentraxin (Narp) as a candidate gene involved in the remodeling or progression of damaged glomeruli. Glomerular Narp mRNA expression was monitored during disease in both Lewis sub strains. Immunohistochemistry revealed that Narp protein is exclusively expressed in Lew/Maa glomeruli 7 and 14 days after induction of anti-Thy-1 nephritis. Double-immunofluorescent staining showed that proliferating mesangial cells and parietal epithelial cells (PECs) at sites of adhesion to podocytes are partially Narp-positive, whereas podocytes fail to express Narp. Immunohistochemistry in nephritic Wistar, unilaterally nephrectomized Wistar and Sprague-Dawley rats showed that Narp protein is present only in strains that develop progressive glomerulosclerosis but never in strains that show remodeling. We conclude that Narp is a predictor for anti-Thy-1 nephritis-induced glomerulosclerosis and its expression by PECs may be involved in the progression to glomerulosclerosis.

Original language	English (US)
Pages (from-to)	1279-1286
Number of pages	8
Journal	Kidney international
Volume	70
Issue number	7
DOIs	https://doi.org/10.1038/sj.ki.5001757
State	Published - Oct 9 2006

Keywords

Gene expression
Glomerular epithelial cells
Glomerulosclerosis
Immunology and pathology
Renal progression

ASJC Scopus subject areas

Nephrology

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10.1038/sj.ki.5001757

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@article{02d46eebcd284001a7647e396e0b3519,

title = "Glomerular expression of neuronal activity-regulated pentraxin precedes the development of anti-Thy-1-induced progressive glomerulosclerosis",

abstract = "Although it is clear that genetic predispositions play a role in progressive glomerulosclerosis, identification of specific genes is difficult because of natural genetic heterogeneity among individuals. We have reported a differential susceptibility to progressive glomerulosclerosis after induction of experimental glomerulonephritis anti-Thy-1 nephritis in Lewis rat substrains. Glomerular lesions in Lewis/M{\o}llegard rats resolve spontaneously, whereas Lewis/Maastricht (Lew/Maa) rats develop progressive glomerulosclerosis. This predisposition for progressive glomerulosclerosis is governed by unknown genes that are expressed by renal cells. Here, differential gene expression analysis using a rat complementary DNA micro array revealed neuronal activity-regulated pentraxin (Narp) as a candidate gene involved in the remodeling or progression of damaged glomeruli. Glomerular Narp mRNA expression was monitored during disease in both Lewis sub strains. Immunohistochemistry revealed that Narp protein is exclusively expressed in Lew/Maa glomeruli 7 and 14 days after induction of anti-Thy-1 nephritis. Double-immunofluorescent staining showed that proliferating mesangial cells and parietal epithelial cells (PECs) at sites of adhesion to podocytes are partially Narp-positive, whereas podocytes fail to express Narp. Immunohistochemistry in nephritic Wistar, unilaterally nephrectomized Wistar and Sprague-Dawley rats showed that Narp protein is present only in strains that develop progressive glomerulosclerosis but never in strains that show remodeling. We conclude that Narp is a predictor for anti-Thy-1 nephritis-induced glomerulosclerosis and its expression by PECs may be involved in the progression to glomerulosclerosis.",

keywords = "Gene expression, Glomerular epithelial cells, Glomerulosclerosis, Immunology and pathology, Renal progression",

author = "Aben, {J. A.} and Ijpelaar, {D. H.} and H. Baelde and P. Worley and N. Noble and Bruijn, {J. A.} and {De Heer}, E.",

note = "Funding Information: This research was supported by the Dutch Kidney Foundation grant C98.1800. We thank Dr Erno Vreugdenhil (Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University, The Netherlands) for sharing the I.M.A.G.E rat cDNA library. We greatly appreciate the helpful suggestions of Dr Tom van Wezel (Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands) and Dr Judith Boer (Leiden Genome Technology Center, Leiden, The Netherlands) in designing the micro array experiments. Furthermore we greatly appreciate the excellent technical assistance of Dennis Hoogervorst, Thirza van den Berg, Annemieke van der Wal and Maria Essers. Part of this study was presented at the 2004 and 2005 annual meeting of the American Society of Nephrology. ",

year = "2006",

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doi = "10.1038/sj.ki.5001757",

language = "English (US)",

volume = "70",

pages = "1279--1286",

journal = "Kidney international",

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T1 - Glomerular expression of neuronal activity-regulated pentraxin precedes the development of anti-Thy-1-induced progressive glomerulosclerosis

AU - Aben, J. A.

AU - Ijpelaar, D. H.

AU - Baelde, H.

AU - Worley, P.

AU - Noble, N.

AU - Bruijn, J. A.

AU - De Heer, E.

N1 - Funding Information: This research was supported by the Dutch Kidney Foundation grant C98.1800. We thank Dr Erno Vreugdenhil (Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University, The Netherlands) for sharing the I.M.A.G.E rat cDNA library. We greatly appreciate the helpful suggestions of Dr Tom van Wezel (Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands) and Dr Judith Boer (Leiden Genome Technology Center, Leiden, The Netherlands) in designing the micro array experiments. Furthermore we greatly appreciate the excellent technical assistance of Dennis Hoogervorst, Thirza van den Berg, Annemieke van der Wal and Maria Essers. Part of this study was presented at the 2004 and 2005 annual meeting of the American Society of Nephrology.

PY - 2006/10/9

Y1 - 2006/10/9

N2 - Although it is clear that genetic predispositions play a role in progressive glomerulosclerosis, identification of specific genes is difficult because of natural genetic heterogeneity among individuals. We have reported a differential susceptibility to progressive glomerulosclerosis after induction of experimental glomerulonephritis anti-Thy-1 nephritis in Lewis rat substrains. Glomerular lesions in Lewis/Møllegard rats resolve spontaneously, whereas Lewis/Maastricht (Lew/Maa) rats develop progressive glomerulosclerosis. This predisposition for progressive glomerulosclerosis is governed by unknown genes that are expressed by renal cells. Here, differential gene expression analysis using a rat complementary DNA micro array revealed neuronal activity-regulated pentraxin (Narp) as a candidate gene involved in the remodeling or progression of damaged glomeruli. Glomerular Narp mRNA expression was monitored during disease in both Lewis sub strains. Immunohistochemistry revealed that Narp protein is exclusively expressed in Lew/Maa glomeruli 7 and 14 days after induction of anti-Thy-1 nephritis. Double-immunofluorescent staining showed that proliferating mesangial cells and parietal epithelial cells (PECs) at sites of adhesion to podocytes are partially Narp-positive, whereas podocytes fail to express Narp. Immunohistochemistry in nephritic Wistar, unilaterally nephrectomized Wistar and Sprague-Dawley rats showed that Narp protein is present only in strains that develop progressive glomerulosclerosis but never in strains that show remodeling. We conclude that Narp is a predictor for anti-Thy-1 nephritis-induced glomerulosclerosis and its expression by PECs may be involved in the progression to glomerulosclerosis.

AB - Although it is clear that genetic predispositions play a role in progressive glomerulosclerosis, identification of specific genes is difficult because of natural genetic heterogeneity among individuals. We have reported a differential susceptibility to progressive glomerulosclerosis after induction of experimental glomerulonephritis anti-Thy-1 nephritis in Lewis rat substrains. Glomerular lesions in Lewis/Møllegard rats resolve spontaneously, whereas Lewis/Maastricht (Lew/Maa) rats develop progressive glomerulosclerosis. This predisposition for progressive glomerulosclerosis is governed by unknown genes that are expressed by renal cells. Here, differential gene expression analysis using a rat complementary DNA micro array revealed neuronal activity-regulated pentraxin (Narp) as a candidate gene involved in the remodeling or progression of damaged glomeruli. Glomerular Narp mRNA expression was monitored during disease in both Lewis sub strains. Immunohistochemistry revealed that Narp protein is exclusively expressed in Lew/Maa glomeruli 7 and 14 days after induction of anti-Thy-1 nephritis. Double-immunofluorescent staining showed that proliferating mesangial cells and parietal epithelial cells (PECs) at sites of adhesion to podocytes are partially Narp-positive, whereas podocytes fail to express Narp. Immunohistochemistry in nephritic Wistar, unilaterally nephrectomized Wistar and Sprague-Dawley rats showed that Narp protein is present only in strains that develop progressive glomerulosclerosis but never in strains that show remodeling. We conclude that Narp is a predictor for anti-Thy-1 nephritis-induced glomerulosclerosis and its expression by PECs may be involved in the progression to glomerulosclerosis.

KW - Gene expression

KW - Glomerular epithelial cells

KW - Glomerulosclerosis

KW - Immunology and pathology

KW - Renal progression

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U2 - 10.1038/sj.ki.5001757

DO - 10.1038/sj.ki.5001757

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SN - 0085-2538

VL - 70

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EP - 1286

JO - Kidney international

JF - Kidney international

IS - 7

ER -

Glomerular expression of neuronal activity-regulated pentraxin precedes the development of anti-Thy-1-induced progressive glomerulosclerosis

Abstract

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