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- Title
MicroRNA-155 aggravates ischemia–reperfusion injury by modulation of inflammatory cell recruitment and the respiratory oxidative burst.
- Authors
Eisenhardt, Steffen U.; Weiss, Jakob B. W.; Smolka, Christian; Maxeiner, Johanna; Pankratz, Franziska; Bemtgen, Xavier; Kustermann, Max; Thiele, Jan R.; Schmidt, Yvonne; Stark, G. Bjoern; Moser, Martin; Bode, Christoph; Grundmann, Sebastian
- Abstract
The inflammatory sequelae of ischemia-reperfusion injury (IRI) are a major causal factor of tissue injury in various clinical settings. MicroRNAs (miRs) are short, non-coding RNAs, which regulate protein expression. Here, we investigated the role of miR-155 in IR-related tissue injury. Quantifying microRNA-expression levels in a human muscle tissue after IRI, we found miR-155 expression to be significantly increased and to correlate with the increased expression of TNF-α, IL-1β, CD105, and Caspase3 as well as with leukocyte infiltration. The direct miR-155 target gene SOCS-1 was downregulated. In a mouse model of myocardial infarction, temporary LAD ligation and reperfusion injury resulted in a smaller area of necrosis in miR-155-/- animals compared to wildtype animals. To investigate the underlying mechanisms, we evaluated the effect of miR-155 on inflammatory cell recruitment by intravital microscopy and on the generation of reactive oxygen species (ROS) of macrophages. Our intravital imaging results demonstrated a decreased recruitment of inflammatory cells in miR-155-/- animals during IRI. The generation of ROS in leukocytic cells of miR-155-/- animals was also reduced. RNA silencing of the direct miR-155 target gene SOCS-1 abrogated this effect. In conclusion, miR-155 aggravates the inflammatory response, leukocyte infiltration and tissue damage in IRI via modulation of SOCS-1-dependent generation of ROS. MiR-155 is thus a potential target for the treatment or prevention of IRI.
- Publication
Basic Research in Cardiology, 2015, Vol 110, Issue 3, p1
- ISSN
0300-8428
- Publication type
Article
- DOI
10.1007/s00395-015-0490-9