Temporal Regulation of Glomerular and Cortical Tubulointerstitial Genes Involved in the Development of Nephrotoxic Serum Nephritis

Maria E Ougaard, Frederikke E Sembach, Peter H Kvist, Morten Tonnesen, Klaus S Frederiksen, Martin Egfjord, Henrik E Jensen, Elisabeth D Galsgaard

    3 Citationer (Scopus)

    Abstract

    BACKGROUND/AIMS: Murine nephrotoxic nephritis (NTN) is a well-established model resembling chronic kidney disease. Investigating gene expression patterns separately in the glomerular and cortical tubulointerstitial structure could provide new knowledge about structure-specific changes in expression of genes in the NTN model.

    METHODS: Glomerular, cortical tubulointerstitial and whole kidney tissues from mice subjected to nephrotoxic serum (NTS) or phosphate buffered saline (PBS) were collected on day 7, 21 and 42 using laser microdissection (LMD). Total RNA was extracted and subjected to nCounter NanoString. Histology, immunohistochemistry, in situ hybridization and/or quantitative real time PCR (qRT PCR) were performed to confirm regulation of selected genes.

    RESULTS: LMD provided detailed information about genes that were regulated differently between structures over time. Some of the fibrotic and inflammatory genes (Col1a1, Col3a1 and Ccl2) were upregulated in both structures, whereas other genes such as Spp1 and Grem1 were differentially regulated suggesting spatial pathogenic mechanisms in the kidney. Downregulation of cortical tubulointerstitium genes involved in iron metabolism was detected along with iron accumulation.

    CONCLUSION: This study demonstrates several regulated genes in pathways important for the pathogenesis of the NTN model and that LMD identifies structure-specific changes in gene expression during disease development. Furthermore, this study shows the benefits of isolating glomeruli and cortical tubulointerstitium in order to identify gene regulation.

    OriginalsprogEngelsk
    TidsskriftNephron
    Vol/bind140
    Udgave nummer3
    Sider (fra-til)218-230
    Antal sider13
    ISSN0028-2766
    DOI
    StatusUdgivet - 2018

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