The lymphatics have emerged as critical players in the progression and resolution of
inflammation. The goal of this study was to identify specific
microRNAs (
miRNAs) that regulate lymphatic inflammatory processes. Rat mesenteric lymphatic endothelial cells (LECs) were exposed to the proinflammatory
cytokine tumor necrosis factor-α for 2, 24, and 96 h, and
miRNA profiling was carried out by real-time PCR arrays. Our data demonstrate a specific set of
miRNAs that are differentially expressed (>1.8-fold and/or P < 0.05) in LECs in response to
tumor necrosis factor-α and are involved in
inflammation, angiogenesis, endothelial-mesenchymal transition, and cell proliferation and senescence. We further characterized the expression of
miRNA 9 (miR-9) that was induced in LECs and in inflamed rat mesenteric lymphatics. Our results showed that miR-9 overexpression significantly repressed NF-κB expression and, thereby, suppressed
inflammation but promoted LEC tube formation, as well as expression of the prolymphangiogenic molecules
endothelial nitric oxide synthase and
VEGF receptor type 3. LEC viability and proliferation and endothelial-mesenchymal transition were also significantly induced by miR-9. This study provides the first evidence of a distinct profile of
miRNAs associated with LECs during
inflammation. It also identifies the critical dual role of miR-9 in fine-tuning the balance between lymphatic inflammatory and lymphangiogenic pathways.