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Genomic analysis of a mouse model of immunoglobulin A nephropathy reveals an enhanced PDGF–EDG5 cascade

The Pharmacogenomics Journal volume 1, pages 211–217 (2001)Cite this article

Abstract

The molecular mechanism of immunoglobulin A nephropathy (IgAN), the most common primary renal glomerular disease worldwide, is unknown. HIGA (high serum IgA) mouse is a valid model of IgAN showing almost all of the pathological features, including mesangial cell proliferation. Here we elucidate a pattern of gene expression associated with IgAN by analyzing the diseased kidneys on cDNA microarrays. In particular, we showed an enhanced expression of several genes regulating the cell cycle and proliferation, including growth factors and their receptors, as well as endothelial differentiation gene-5 (EDG5), a receptor for sphingosine 1-phosphate (SPP). One of the growth factors, platelet-derived growth factor (PDGF) induces a marked upregulation of EDG5 in proliferative mesangial cells, and promotes cell proliferation synergistically with SPP. The genomic approach allows us to identify families of genes involved in a process, and can indicate that enhanced PDGF-EDG5 signaling plays an important role in the progression of IgAN.

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Acknowledgements

We thank Drs S Stojilkovic (National Institute of Child Health and Human Development, National Institutes of Health) and GE Smyth (Research Laboratories, Nippon Shinyaku Co) for critical reading of the manuscript. This work was supported in part by research grants from the Scientific Fund of the Ministry of Education, Science, and Culture of Japan, the Japan Health Science Foundation and Ministry of Human Health and Welfare, the Organization for Pharmaceutical Safety and Research (OPSR), and a Grant for Liberal Harmonious Research Promotion System from the Science and Technology Agency.

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Authors and Affiliations

  1. Department of Molecular, Cell Pharmacology, National Children's Medical Research Center, Setagaya-ku, Tokyo, Japan

    S Katsuma, S Shiojima, A Hirasawa, Y Suzuki & G Tsujimoto

  2. Research Laboratories, Nippon Shinyaku Co, Tsukuba, Ibaraki, Japan

    K Takagaki, M Murai, Y Kaminishi, Y Hada, M Koba, S Miyawaki, T Ohgi & J Yano

  3. Department of Cardiovascular Medicine, Kyoto University, Graduate School of Medicine, Kyoto, Japan

    E Muso

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  1. S Katsuma
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Correspondence to G Tsujimoto.

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Katsuma, S., Shiojima, S., Hirasawa, A. et al. Genomic analysis of a mouse model of immunoglobulin A nephropathy reveals an enhanced PDGF–EDG5 cascade. Pharmacogenomics J 1, 211–217 (2001). https://doi.org/10.1038/sj.tpj.6500043

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  • DOI: https://doi.org/10.1038/sj.tpj.6500043

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