MicroRNA signature of inflamed lymphatic endothelium and role of miR-9 in lymphangiogenesis and inflammation.
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.
Department of Medical Physiology, Texas A & M Health Science Center, College of Medicine, Temple, Texas; and.
Sanjukta
S
Chakraborty
Department of Medical Physiology, Texas A & M Health Science Center, College of Medicine, Temple, Texas; and.
David C
DC
Zawieja
Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, Missouri.
Michael J
MJ
Davis
Department of Medical Physiology, Texas A & M Health Science Center, College of Medicine, Temple, Texas; and marim@tamu.edu.
Mariappan
M
Muthuchamy
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D007249:Inflammation / Q000378:metabolism*; D042583:Lymphangiogenesis / Q000235:genetics / Q000502:physiology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D016207:Cytokines; C582333:MIRN9 microRNA, rat; D035683:MicroRNAs
inflammation; lymphangiogenesis; lymphatic endothelial cell; microRNA; signaling