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Der Transkriptionsfaktor Egr-1 reguliert das Wachstum glomerulärer Mesangiumzellen

The transcriptional regulator Egr-1 and growth control of glomerular mesangial cells

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Zusammenfassung

Hintergrund

Der Transkriptionsfaktor Early-growth-response-gene-1 (Egr-1) wird in kultivierten glomerulären Mesangiumzellen (MZ) der Niere durch verschiedene Mitogene schnell und transient induziert.

Methode und Ergebnisse

Hier zeigen wir, daß es auch in vivo, im Modell einer mesangioproliferativen Glomerulonephritis (GN), zu einer Hochregulierung von Egr-1 kommt. Im Northern Blot fand sich ein 14,9facher Anstieg der Egr-1-mRNA am Tag 6 der Glomerulonephritis. Mittels Immunzytochemie wurde gleichzeitig ein Anstieg an Egr-1-Protein gemessen. Egr-1 war dabei vorwiegend nukleär und in mesangialer Lokalisation nach-weisbar. Um zu testen, ob Egr-1 direkt die Mesangiumzellproliferation reguliert, präinkubierten wir kultivierte Mesangiumzellen mit gegen Egr-1 gerichteten Antisense-Oligonucleotiden. Es zeigte sich eine deutliche Hemmung des Platelet-Derived-Growth-Factor-(PDGF-)induzierten Anstiegs von Egr-1-mRNA und-Protein um 75%, bzw. 74%. Gleichzeitig hemmten Egr-1 antisense Oligonucleotide dosisabhängig die PDGF-induzierte Mesangiumzellproliferation, gemessen mittels Thymidinaufnahme, um maximal 75%. Entsprechende Kontrolloligonucleotide hatten keinen Einfluß auf Egr-1-mRNA,-Protein oder Mesangiumzellenwachstum.

Schlußfolgerung

Egr-1 ist demzufolge ein notwendiger Bestandteil der mitogenen Signalübermittlung in glomerulären Mesangiumzellen der Niere.

Summary

Background

The transcriptional regulator Early growth response gene-1 (Egr-1) is rapidly and transiently induced by various mitogens in cultured rat mesangial cells (MCs).

Method and Results

Here we show Egr-1 induction in an in vivo model of mesangioproliferative glomerulonephritis (GN). A 14.9-fold increase in Egr-1 mRNA was observed 6 days after disease induction. A concomitant increase in Egr-1 protein was demonstrated by immunocytochemistry. Egr-1 was mainly localized to the nuclei of cells in mesangial localization. To test whether Egr-1 directly regulated MC proliferation, we preincubated cultured MCs with antisense oligonucleotides directed against Egr-1. The platelet-derived growth factor (PDGF)-induced increase in Egr-1 mRNA and protein levels was inhibited by 75% and 74%, respectively. At the same time Egr-1 antisense oligonucleotides dose-dependently inhibited MC-proliferation as determined by thymidine-uptake by up to 75%. Control oligonucleotides were without effects on Egr-1 mRNA, protein or MC growth.

Conclusion

We conclude that Egr-1 induction is a necessary step in the mitogenic signaling cascade in glomerular MCs.

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Authors and Affiliations

  1. Medizinische Klinik IV-Nephrologische, Forschungslabors der Universität, Loschgestraße 8, D-91054, Erlangen

    Harald D. Rupprecht, Gerhard Hofer, R. Bernd Sterzel & Harald O. Schöcklmann

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  1. Harald D. Rupprecht
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  2. Gerhard Hofer
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  3. R. Bernd Sterzel
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  4. Harald O. Schöcklmann
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Rupprecht, H.D., Hofer, G., Sterzel, R.B. et al. Der Transkriptionsfaktor Egr-1 reguliert das Wachstum glomerulärer Mesangiumzellen. Med. Klin. 92, 68–73 (1997). https://doi.org/10.1007/BF03042287

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  • DOI: https://doi.org/10.1007/BF03042287

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