1.Introduction
MiRNAs are a class of small, endogenous, non-coding RNAs approximately 18 to 25 nucleotides in length, which regulate the gene expression at the transcriptional level (1, 2). More than 50% of the mammalian protein-coding genes are regulated by miRNAs(1). In addition, miRNAs are widely involved in ischemia reperfusion IR injury, innate and adaptive immune responses, inflammatory response and cancer (3, 4). Although studies have demonstrated that miRNAs can regulate target gene expression following lung transplantation (LT) (5), global study identified the differentially expressed (DE) miRNAs in response to IR injury following LT.
Recently, millions of short sequence reads were identified using Illumina high-throughput sequencing (HiSeq) (6, 7). Moreover, the technique has been widely used to detect the miRNA expression profile in several species and shown high-quality results in identification of known and novel miRNAs. The HiSeq platform can also be used to predict the target genes and their corresponding biological functions (8).
MiRNA-122, a liver-specific miRNA, has been known to reduce the invasiveness and metastasis in non-small cell lung cancer (NECLC) (9). The expression of miRNA-122 has been reported to be significantly elevated during liver IR injury (10).Similarly, our previous studies have reported increased expression of miRNA-122 following LT. However, the functional role and the underlying molecular mechanisms of miRNA-122 in IR injury following LT remain unclear.
Toll-like receptors (TLRs) are highly conserved molecules that are abundantly presented on the surface of several inflammatory cells including alveolar macrophages, endothelial cells, and dendritic cells. MiRNAs are known to can regulate the inflammatory process through the TLR signaling pathway (11, 12). In addition, TLRs contribute to inflammation during IR injury (13) and are associated with acute lung injury (14). In the present study, we explored the functions of miRNA-122 and the TLR pathway in IR injury following LT using a mouse model.