MicroRNAs in Immunität und Organtransplantation

Zusammenfassung

Die Transplantation von Organen hat in der heutigen Hochleistungsmedizin einen bedeutenden Stellenwert eingenommen. Die Entwicklung hocheffektiver Immunsuppressiva und damit die Verhinderung einer Abstoßung ist die Voraussetzung für das akute und langfristige Transplantatüberleben. Trotz dieser enormen Entwicklung ist die Rate an Organverlusten durch akute und chronische Rejektion immer noch sehr hoch. Verschiedene Biomarker der Transplantatabstoßung konnten bisher identifiziert werden, deren Nutzbarkeit ist jedoch bis heute nur von mäßigem Erfolg. Kürzlich sind kleine regulatorische RNA-Moleküle, sogenannte microRNAs, in den Fokus der Forschung gerückt. MicroRNAs (miRNAs) sind kurze, nicht kodierende RNA-Moleküle, die zur Repression von Zielgenen führen durch einen posttranskriptionellen Abbau von Messenger-RNA (mRNA) und/oder translationaler Inhibition der Proteinexpression. Einige Studien konnten bisher zeigen, dass diese regulatorischen RNA-Moleküle als wichtige Biomarker genutzt werden können. In diesem Übersichtsartikel fassen wir das aktuelle Wissen über die Rolle von microRNAs in der immunologischen Regulation der Transplantathomöostase zusammen. Zudem stellen wir die molekularen Mechanismen und therapeutischen Implikationen sogenannter miRNA-Antagonisten (AntagomiRs) vor, die zu einer zukünftigen potenziellen Verhinderung der Abstoßung und daraus resultierenden Verbesserung des Organüberlebens führen könnten.

Abstract

Due to the development of highly effective immunosuppressive agents over the past 20 years organ transplantation has evolved into a standard therapeutic intervention once organ function terminally declines. Even though the incidence of acute and chronic rejection has been successfully reduced, it still poses a serious life-threatening complication. Several different biomarkers of acute and chronic rejection have been investigated thus far. In recent years microRNAs have come into focus as powerful regulators of gene expression. MicroRNAs (miRNAs) are small, non-coding RNAs that lead to the repression of target genes through the post-transcriptional degradation of messenger-RNA (mRNA) and translational inhibition of protein expression. MiRNAs in different species are highly conserved. MiRNAs regulate the expression of a variety of genes including those involved in adaptive immunity. It has been described that approx. 1500 miRNAs regulate about 50% of the human genome. Therefore, miRNAs might also be involved in the altered expression pattern of genes implicated in acute and chronic rejection. Several studies have elucidated the potential of microRNAs as biomarkers of diseases. We here outline the role of microRNA in transplant homeostasis and organ rejection. In addition, we introduce microRNA antagonists (AntagomiRs) as potential therapeutic agents in the prevention of organ rejection.

Schlüsselwörter

Immunität - microRNAs - Organtransplantation - Rejektion

Key words

immunity - microRNA - organ transplantation - rejection

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