Expression profiles and circulation dynamics of rat mesenteric lymph microRNAs

Mesenteric lymph is vital for immune cell trafficking and intestinal fluid and chyle transport, which aid homeostatic maintenance. There have been few reports investigating the profiles and circulatory dynamics of mesenteric lymph microRNAs (miRNAs). The present study aimed to provide a comprehensive analysis of miRNAs in normal rodent mesenteric lymph. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR)-based array analysis was performed to examine the expression levels of 375 miRNAs in normal rat mesenteric lymph. Using differential centrifugation, the presence of miR-150, a representative lymph miRNA, in exosomes was assessed. Rat small intestine epithelial cell line IEC-6-derived exosomes were prepared from culture supernatants of cells transfected with cel-miR-238-3p, and were used to trace the administered exosomes in vivo and to investigate the in vivo delivery of lymph miRNAs via mesenteric lymphatics into the systemic circulation following injection of cel-miR-238-3p-exosomes. RT-qPCR-based array analysis detected 287 miRNAs in lymph, and 21 miRNAs that were significantly differentially expressed between lymph and plasma. Lymph fractionation analysis demonstrated that some cell-free lymph miR-150 was distributed in the exosome-containing microsomal fraction. Furthermore, in vivo analysis of lymph miRNA delivery revealed that exosomal cel-miR-238-3p was markedly distributed in the lung compared with in the liver, kidney and spleen, thus indicating that the lung is the major organ responsible for clearance of exosomal lymph miRNAs. These findings provide novel insights into the modulation of gene expression by mesenteric lymph miRNAs in the lung.