MiRNA-122 promotes ischemia-reperfusion injury after lung
transplantation via the TLR signaling pathway
Abstract
Background: MiRNAs have been recently implicated in the pathogenesis
underlying ischemia-reperfusion (IR) injury. We investigated the miRNAs
expression profiles in the early stages after lung transplantation (LT)
and studied the involvement of Toll-like receptor(TLR) signaling pathway
in lung IR injury following LT. Methods: We established the left LT
model in mice, The mice were injected with a miRNA-122 specific
inhibitor, following which pathological changes in the lung tissue were
studied using different lung injury indicators. In addition, we
performed deep sequencing in transplanted lung tissues to indentify
differentially expressed (DE) miRNAs and their target genes. Results: A
total of 12DE miRNAs were selected and 2,476 target genes were
identified; The gene ontology (GO) enrichment analysis predicted 6,063
terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis
predicted 1,554 biological pathways. Compared with the control group,
inhibiting the expression of miRNA-122 significantly reduced the lung
injury and lung W / D ratio (p<0.05). In addition, the
activity of myeloperoxidase (MPO) and expression of tumor necrosis
factor (TNF)-α and TLR2/4 decreased (p<0.05); whereas the
expression of interleukin-10(IL-10) expression levels increased
(p<0,05). Furthermore, the inhibition of miRNA-122 suppressed
the IR injury-induced activation of the TLR signaling pathway.
Conclusions: Our findings showed the differential expression of several
miRNAs in the early inflammatory response following LT. Of these,
miRNA-122 promoted the IR injury following LT, whereas its inhibition
prevented IR injury in a TLR-dependent manner.