MicroRNAs in the Lymphatic Endothelium: Master Regulators of Lineage Plasticity and Inflammation

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2017 Feb 25

PMID 28232833

Citations 6

Authors

Daniel Yee

Mark C Coles

Dimitris Lagos

Affiliations

Soon will be listed here.

Abstract

microRNAs (miRNAs) are highly conserved, small non-coding RNAs that regulate gene expression at the posttranscriptional level. They have crucial roles in organismal development, homeostasis, and cellular responses to pathological stress. The lymphatic system is a large vascular network that actively regulates the immune response through antigen trafficking, cytokine secretion, and inducing peripheral tolerance. Here, we review the role of miRNAs in the lymphatic endothelium with a particular focus on their role in lymphatic endothelial cell (LEC) plasticity, inflammation, and regulatory function. We highlight the lineage plasticity of LECs during inflammation and the importance of understanding the regulatory role of miRNAs in these processes. We propose that targeting miRNA expression in lymphatic endothelium can be a novel strategy in treating human pathologies associated with lymphatic dysfunction.

Citing Articles

Inhibition of Lymphangiogenesis: A Protective Role of microRNA 146a-5p in Breast Cancer.

Liang W, Wang H, Fu B, Song Y, Zhang Z, Liu X Breast J. 2025; 2024:7813083.

PMID: 39742358 PMC: 11357816. DOI: 10.1155/2024/7813083.

miR-31-5p-Modified RAW 264.7 Macrophages Affect Profibrotic Phenotype of Lymphatic Endothelial Cells In Vitro.

Moskalik A, Ratajska A, Majchrzak B, Jankowska-Steifer E, Bartkowiak K, Bartkowiak M Int J Mol Sci. 2022; 23(21).

PMID: 36361979 PMC: 9657882. DOI: 10.3390/ijms232113193.

Endothelial Microparticle-Mediated Transfer of microRNA-19b Inhibits the Function and Distribution of Lymphatic Vessels in Atherosclerotic Mice.

Yu S, Cui Y, Song Z, Li S, Zhang C, Song J Front Physiol. 2022; 13:850298.

PMID: 35615671 PMC: 9124754. DOI: 10.3389/fphys.2022.850298.

Role of Podoplanin-Positive Cells in Cardiac Fibrosis and Angiogenesis After Ischemia.

Cimini M, Kishore R Front Physiol. 2021; 12:667278.

PMID: 33912076 PMC: 8072458. DOI: 10.3389/fphys.2021.667278.

Placental exosome-mediated Bta-miR-499-Lin28B/let-7 axis regulates inflammatory bias during early pregnancy.

Zhao G, Yang C, Yang J, Liu P, Jiang K, Shaukat A Cell Death Dis. 2018; 9(6):704.

PMID: 29899331 PMC: 5999645. DOI: 10.1038/s41419-018-0713-8.

References

Bernstein E, Kim S, Carmell M, Murchison E, Alcorn H, Li M . Dicer is essential for mouse development. Nat Genet. 2003; 35(3):215-7. DOI: 10.1038/ng1253. View

Taganov K, Boldin M, Chang K, Baltimore D . NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A. 2006; 103(33):12481-6. PMC: 1567904. DOI: 10.1073/pnas.0605298103. View

Oliver G . Lymphatic vasculature development. Nat Rev Immunol. 2004; 4(1):35-45. DOI: 10.1038/nri1258. View

Kuehbacher A, Urbich C, Zeiher A, Dimmeler S . Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis. Circ Res. 2007; 101(1):59-68. DOI: 10.1161/CIRCRESAHA.107.153916. View

Vigorito E, Perks K, Abreu-Goodger C, Bunting S, Xiang Z, Kohlhaas S . microRNA-155 regulates the generation of immunoglobulin class-switched plasma cells. Immunity. 2007; 27(6):847-59. PMC: 4135426. DOI: 10.1016/j.immuni.2007.10.009. View

Petrova T, Makinen T, Makela T, Saarela J, Virtanen I, Ferrell R . Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor. EMBO J. 2002; 21(17):4593-9. PMC: 125413. DOI: 10.1093/emboj/cdf470. View

Srinivasan R, Geng X, Yang Y, Wang Y, Mukatira S, Studer M . The nuclear hormone receptor Coup-TFII is required for the initiation and early maintenance of Prox1 expression in lymphatic endothelial cells. Genes Dev. 2010; 24(7):696-707. PMC: 2849126. DOI: 10.1101/gad.1859310. View

Trevaskis N, Kaminskas L, Porter C . From sewer to saviour - targeting the lymphatic system to promote drug exposure and activity. Nat Rev Drug Discov. 2015; 14(11):781-803. DOI: 10.1038/nrd4608. View

Seo M, Choi J, Rho C, Joo C, Lee S . MicroRNA miR-466 inhibits Lymphangiogenesis by targeting prospero-related homeobox 1 in the alkali burn corneal injury model. J Biomed Sci. 2015; 22:3. PMC: 4304626. DOI: 10.1186/s12929-014-0104-0. View

10.

Kataru R, Jung K, Jang C, Yang H, Schwendener R, Baik J . Critical role of CD11b+ macrophages and VEGF in inflammatory lymphangiogenesis, antigen clearance, and inflammation resolution. Blood. 2009; 113(22):5650-9. DOI: 10.1182/blood-2008-09-176776. View

11.

Kataru R, Kim H, Jang C, Choi D, Koh B, Kim M . T lymphocytes negatively regulate lymph node lymphatic vessel formation. Immunity. 2011; 34(1):96-107. DOI: 10.1016/j.immuni.2010.12.016. View

12.

Bazigou E, Xie S, Chen C, Weston A, Miura N, Sorokin L . Integrin-alpha9 is required for fibronectin matrix assembly during lymphatic valve morphogenesis. Dev Cell. 2009; 17(2):175-86. PMC: 2747264. DOI: 10.1016/j.devcel.2009.06.017. View

13.

Yanez J, Wang S, Knemeyer I, Wirth M, Alton K . Intestinal lymphatic transport for drug delivery. Adv Drug Deliv Rev. 2011; 63(10-11):923-42. PMC: 7126116. DOI: 10.1016/j.addr.2011.05.019. View

14.

Flister M, Wilber A, Hall K, Iwata C, Miyazono K, Nisato R . Inflammation induces lymphangiogenesis through up-regulation of VEGFR-3 mediated by NF-kappaB and Prox1. Blood. 2009; 115(2):418-29. PMC: 2808162. DOI: 10.1182/blood-2008-12-196840. View

15.

Podgrabinska S, Kamalu O, Mayer L, Shimaoka M, Snoeck H, Randolph G . Inflamed lymphatic endothelium suppresses dendritic cell maturation and function via Mac-1/ICAM-1-dependent mechanism. J Immunol. 2009; 183(3):1767-79. PMC: 4410990. DOI: 10.4049/jimmunol.0802167. View

16.

Jackson D . Biology of the lymphatic marker LYVE-1 and applications in research into lymphatic trafficking and lymphangiogenesis. APMIS. 2004; 112(7-8):526-38. DOI: 10.1111/j.1600-0463.2004.apm11207-0811.x. View

17.

Hong Y, Foreman K, Shin J, Hirakawa S, Curry C, Sage D . Lymphatic reprogramming of blood vascular endothelium by Kaposi sarcoma-associated herpesvirus. Nat Genet. 2004; 36(7):683-5. DOI: 10.1038/ng1383. View

18.

Heyam A, Lagos D, Plevin M . Dissecting the roles of TRBP and PACT in double-stranded RNA recognition and processing of noncoding RNAs. Wiley Interdiscip Rev RNA. 2015; 6(3):271-89. PMC: 7169789. DOI: 10.1002/wrna.1272. View

19.

Lagos D, Pollara G, Henderson S, Gratrix F, Fabani M, Milne R . miR-132 regulates antiviral innate immunity through suppression of the p300 transcriptional co-activator. Nat Cell Biol. 2010; 12(5):513-9. DOI: 10.1038/ncb2054. View

20.

Leslie Pedrioli D, Karpanen T, Dabouras V, Jurisic G, van de Hoek G, Shin J . miR-31 functions as a negative regulator of lymphatic vascular lineage-specific differentiation in vitro and vascular development in vivo. Mol Cell Biol. 2010; 30(14):3620-34. PMC: 2897549. DOI: 10.1128/MCB.00185-10. View