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Expression profiles of congenital renal dysplasia reveal new insights into renal development and disease

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Abstract

Congenital renal dysplasia (RD) is a major cause of renal failure in the pediatric population. Although molecular and genetic aspects of RD have been studied in animal models, limited studies have been done in human RD primarily due to lack of available material. To identify novel genes that are associated with RD and normal kidney development, we performed microarray analysis on total RNA extracted from age-matched fetal kidneys of normal and RD patients. In midgestational RD kidneys, we found 180 upregulated and 104 downregulated transcripts compared with normal kidneys. Among the increased transcripts in the dysplastic kidneys were matrix-degrading enzymes (MMP7, MMP19, TIMP1), inflammation- and immunity-related genes, and growth factors. Expression of genes known to be essential for normal kidney development, such as WT1, BMP7, renin, angiotensin receptor 2 (AGTR2), SAL-like 1 (SALL1) and glypican 3 (GPC3), were decreased in dysplastic kidneys. Expression of selected gene products (BMP7, renin, and MMP7) was further confirmed in parallel sections and in several normal and human dysplastic kidneys, supporting the role of these genes as putative RD biomarkers. These results are among the first to reveal disrupted expression profiles during gestation in human RD patients.

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Acknowledgments

We thank Drs. George Steinhardt at Urologic Consultants, Grand Rapids, MI, USA, and Dr. Edith Schmidt at Sunrise Children’s Hospital, Las Vegas, ND, USA, for their kind contribution of pathologic samples for this study, and Mark Watson at the GeneChip core facility at Washington University St. Louis, for help with the arrays. The study was in part supported by a grant by the Midwest Stone Institute to H. Liapis (# 93267/03), and by NIH-NICHD to S. Jain (HD047396).

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Authors and Affiliations

  1. Department of Medicine (Renal Division), Washington University School of Medicine, Saint Louis, MO, 63110, USA

    Sanjay Jain

  2. Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, 63110, USA

    Adrian A. Suarez & Helen Liapis

  3. Department of Pediatrics, Washington University School of Medicine, Saint Louis, MO, 63110, USA

    John McGuire

  4. Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8118, Saint Louis, MO, 63110-1093, USA

    Helen Liapis

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  1. Sanjay Jain
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Corresponding author

Correspondence to Helen Liapis.

Electronic supplementary material

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Supplementary Table 1

Demographic and pathologic data of kidneys used for microarray analysis (DOC 38 kb)

Supplementary Table 2

Rank ordered list of genes identified by SAM that are upregulated in midgestational normal fetal kidneys compared to late gestation (32–34 week) normal fetal kidneys (DOC 23 kb)

Supplementary Table 3

Rank ordered list of genes identified by SAM that are upregulated in late gestation normal (32–34 week) fetal kidneys compared to mid gestation normal fetal kidneys (DOC 33 kb)

Supplementary Figure 1

Validation of BMP7, MMP7 and Renin expression in normal and dysplastic kidneys in additional samples that were not used in microarray analysis (DOC 196 kb)

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Jain, S., Suarez, A.A., McGuire, J. et al. Expression profiles of congenital renal dysplasia reveal new insights into renal development and disease. Pediatr Nephrol 22, 962–974 (2007). https://doi.org/10.1007/s00467-007-0466-6

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  • DOI: https://doi.org/10.1007/s00467-007-0466-6

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