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In situ expression of connective tissue growth factor in human crescentic glomerulonephritis

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Abstract

Connective tissue growth factor (CTGF) has recently been recognized as an important profibrotic factor and is up-regulated in various renal diseases with fibrosis. The present study describes the sequential localization of CTGF mRNA and its association with transforming growth factor (TGF)-β1 in human crescentic glomerulonephritis (CRGN). Furthermore, we examined the phenotype of CTGF-expressing cells using serial section analysis. Kidney biopsy specimens from 18 CRGN patients were examined using in situ hybridization and immunohistochemistry. CTGF mRNA was expressed in the podocytes and parietal epithelial cells (PECs) in unaffected glomeruli. In addition, it was strongly expressed in the cellular and fibrocellular crescents, particularly in pseudotubule structures. Serial sections revealed that the majority of CTGF mRNA-positive cells in the crescents co-expressed the epithelial marker cytokeratin, but not a marker for macrophages. Moreover, TGF-β1, its receptor TGF-β receptor-I, and extracellular matrix molecules (collagen type I and fibronectin) were co-localized with CTGF mRNA-positive crescents. Our results suggest that CTGF is involved in extracellular matrix production in PECs and that it is one of the mediators promoting the scarring process in glomerular crescents.

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Acknowledgements

This work was supported by grants from the University of Tsukuba, Showa University, and Health Sciences Research Grants of Japan (Research on Specific Diseases of the Nephro-urological Study Group).

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Authors and Affiliations

  1. Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Tennodai 1-1-1, 305-8575, Tsukuba, Ibaraki, Japan

    Katsuyoshi Kanemoto, Joichi Usui & Michio Nagata

  2. Department of Nephrology, Matsuyama Red Cross Hospital, Matsuyama, Ehime, Japan

    Atsumi Harada

  3. Department of Pathology, Kidney Center, Tokyo Women’s Medical University, Tokyo, Japan

    Kosaku Nitta & Shigeru Horita

  4. Department of Nephrology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

    Akio Koyama

  5. Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Jan Aten

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  1. Katsuyoshi Kanemoto
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  2. Joichi Usui
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  3. Kosaku Nitta
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  4. Shigeru Horita
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  8. Michio Nagata
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Correspondence to Michio Nagata.

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Kanemoto, K., Usui, J., Nitta, K. et al. In situ expression of connective tissue growth factor in human crescentic glomerulonephritis. Virchows Arch 444, 257–263 (2004). https://doi.org/10.1007/s00428-003-0959-z

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  • DOI: https://doi.org/10.1007/s00428-003-0959-z

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