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01.04.2013 | Original Article

Comprehensive analysis of glomerular mRNA expression of pro- and antithrombotic genes in atypical haemolytic-uremic syndrome (aHUS)

verfasst von: Friedrich Modde, Putri Andina Agustian, Juliane Wittig, Maximilian Ernst Dämmrich, Vinzent Forstmeier, Udo Vester, Thurid Ahlenstiel, Kerstin Froede, Ulrich Budde, Anne-Margret Wingen, Anke Schwarz, Svjetlana Lovric, Jan Thomas Kielstein, Carsten Bergmann, Nadine Bachmann, Mato Nagel, Hans Heinrich Kreipe, Verena Bröcker, Clemens Luitpold Bockmeyer, Jan Ulrich Becker

Erschienen in: Virchows Archiv | Ausgabe 4/2013

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Abstract

Atypical haemolytic–uremic syndrome (aHUS) is, in most cases, due to hereditary or acquired defects in complement regulation and a life-threatening disease. Despite the rapidly grown knowledge about the primary defects in aHUS, the pathogenesis that links complement dysregulation with microthrombus formation in aHUS is still unknown. Thus, we examined the glomerular microvascular expression of pro- and antithrombotic genes. Glomeruli were microdissected from 12 archival paraffin-embedded biopsies with aHUS and from seven control biopsies. Glomerular mRNA expression was quantified by single real-time PCR reactions after preamplification. In addition immunostains were performed for plasminogen activator inhibitor 1 (PAI-1) and for tissue plasminogen activator (tPA). Results were compared between cases and controls and with clinical data. Glomeruli in aHUS had increased mRNA expression of antifibrinolytic, prothrombotic PAI-1, antithrombotic thrombomodulin (THBD) and CD73 and decreased expression of profibrinolytic, antithrombotic tPA compared to controls. Impaired fibrinolysis due to increased microvascular expression of the antifibrinolytic PAI-1 in combination with the decreased expression of the profibrinolytic tPA seems to be a final common pathway in renal thrombotic microangiopathy that is also effective in aHUS. The concomitant induction of antithrombotic transcripts likely indicates counterregulatory efforts, demonstrating that the capillary bed is not a passive victim of complement attack. Future research should investigate if and how complement activation could induce the reported shift in the expression of PAI-1 and tPA.

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Titel: Comprehensive analysis of glomerular mRNA expression of pro- and antithrombotic genes in atypical haemolytic-uremic syndrome (aHUS)
verfasst von: Friedrich Modde
Putri Andina Agustian
Juliane Wittig
Maximilian Ernst Dämmrich
Vinzent Forstmeier
Udo Vester
Thurid Ahlenstiel
Kerstin Froede
Ulrich Budde
Anne-Margret Wingen
Anke Schwarz
Svjetlana Lovric
Jan Thomas Kielstein
Carsten Bergmann
Nadine Bachmann
Mato Nagel
Hans Heinrich Kreipe
Verena Bröcker
Clemens Luitpold Bockmeyer
Jan Ulrich Becker
Publikationsdatum: 01.04.2013
Verlag: Springer-Verlag
Erschienen in: Virchows Archiv / Ausgabe 4/2013
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-013-1386-4

Springer Medizin

Comprehensive analysis of glomerular mRNA expression of pro- and antithrombotic genes in atypical haemolytic-uremic syndrome (aHUS)

Abstract

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie

Springer Medizin

Abstract

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