Junb controls lymphatic vascular development in zebrafish via miR-182

Kiesow, Kristin; Bennewitz, Katrin; Gutierrez-Miranda, Laura; Stoll, Sandra J.; Hartenstein, Bettina; Angel, Peter; Krøll, Jens; Schorpp-Kistner, Marina

doi:10.1038/srep15007

Cited by 26 publications

(26 citation statements)

References 66 publications

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“…In agreement, loss of JunB in zebrafish resulted in the formation of parachordal lymphangioblasts (Kiesow et al, 2015), and Foxo1 expression reportedly effected EC migration, sprouting and tube formation (Potente et al, 2005). However, the present microarray analysis showed no upregulation of Foxo1 during neurovascular interactions (data not shown), suggesting that the JunB-miR-182-Foxo1 axis is not involved in JunB-mediated neurovascular juxtapositional alignment.…”

Section: Discussionmentioning

confidence: 31%

JunB regulates angiogenesis and neurovascular parallel alignment in mouse embryonic skin

Yoshitomi

Ikeda

Saito

et al. 2017

Journal of Cell Science

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Blood vessels and nerve fibers are often closely arranged in parallel throughout the body. Therefore, neurovascular interactions have been suggested to be important for the development of vascular networks. However, the molecular mechanisms and genes regulating this process remain unclear. In the present study, we investigated the genes that are activated in endothelial cells (ECs) following interactions with neurons during vascular development. Microarray analyses of human primary microvascular ECs co-cultured with mouse primary dorsal root ganglion cells showed that JunB is strongly upregulated in ECs by neurovascular interactions. Furthermore, the forced expression of JunB in ECs stimulated a tip-like cell formation and angiogenesis in vitro and induced vascular endothelial growth factor A (VEGFA) and the pro-angiogenic integrin subunit ITGB3 expression. Moreover, in vivo knockdown of JunB in ECs from developing mouse limb skin considerably decreased the parallel alignments of blood vessels and nerve fibers. Taken together, the present data demonstrates for the first time that JunB plays an important role in the formation of embryonic vascular networks. These results contribute to the molecular understanding of neurovascular interactions during embryonic vascular development.

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Section: Discussionmentioning

confidence: 31%

JunB regulates angiogenesis and neurovascular parallel alignment in mouse embryonic skin

Yoshitomi

Ikeda

Saito

et al. 2017

Journal of Cell Science

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“…Consistently, in the vascular field, JunB was identified as a positive mediator of vasculogenesis and homeostasis but as a negative mediator of cell proliferation and apoptosis. For example, the JunB/miR-128/Foxo1 regulatory axis was shown to govern the development of lympathic vessels in zebrafish 29 , whereas endothelial-specific ablation of JunB mediated by Tie-2 cre resulted in embryonic lethality at E10.5 with embryos exhibiting abnormal vascular structures 30 . However, studies of the role of JunB in heart diseases have been limited.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA 199a-5p induces apoptosis by targeting JunB

Yan

Yang

Meng

et al. 2018

Sci Rep

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MicroRNAs participate in a variety of physiological and pathophysiological processes in various organs including the heart. Our previous work revealed that the level of miR-199a-5p was significantly higher in failing hearts than in control hearts. However, whether it is associated with the progression of heart failure (HF) and mediates cardiomyocyte apoptosis remained unclear. In the present study, we used various biochemical and molecular biological approaches to investigate the changes in miR-199a-5p levels in failing hearts in a rat model induced by acute myocardial infarction. We found that miR-199a-5p levels in the heart increased with the progression of HF, and overexpression of miR-199a-5p significantly increased apoptosis in untreated H9C2 cells and potentiated angiotensin II-induced apoptosis. Thus, our results indicate that miR-199a-5p is involved in the progression of HF and mediates cardiomyocyte apoptosis. We also confirmed that JunB, a member of the activator protein-1 transcription factor family, is one of direct targets of miR-199a-5p via a dual-luciferase reporter assay and mutagenesis on the 3′ untranslated region of the JunB gene. Consistent with the above findings, overexpression of JunB in H9c2 cells suppressed cell apoptosis. Based on our findings, miR-199a-5p induces apoptosis by targeting JunB.

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“… 37 , 38 Another target FOXO1 is required for proper lymphatic vascular development. 39 Variants in or near FOXO1 have recently been associated with central cornea thickness, which is a risk factor for glaucoma. 40 – 42 On the other hand, FOXO1, as a direct target of FOXC1, is involved in maintaining the cellular homeostasis and resistance to oxidative stress in the eye, while FOXC1 sequence variants have been associated with POAG.…”

Section: Discussionmentioning

confidence: 99%

A Common Variant in MIR182 Is Associated With Primary Open-Angle Glaucoma in the NEIGHBORHOOD Consortium

Liu

Bailey

Helwa

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PurposeNoncoding microRNAs (miRNAs) have been implicated in the pathogenesis of glaucoma. We aimed to identify common variants in miRNA coding genes (MIR) associated with primary open-angle glaucoma (POAG).MethodsUsing the NEIGHBORHOOD data set (3853 cases/33,480 controls with European ancestry), we first assessed the relation between 85 variants in 76 MIR genes and overall POAG. Subtype-specific analyses were performed in high-tension glaucoma (HTG) and normal-tension glaucoma subsets. Second, we examined the expression of miR-182, which was associated with POAG, in postmortem human ocular tissues (ciliary body, cornea, retina, and trabecular meshwork [TM]), using miRNA sequencing (miRNA-Seq) and droplet digital PCR (ddPCR). Third, miR-182 expression was also examined in human aqueous humor (AH) by using miRNA-Seq. Fourth, exosomes secreted from primary human TM cells were examined for miR-182 expression by using miRNA-Seq. Fifth, using ddPCR we compared miR-182 expression in AH between five HTG cases and five controls.ResultsOnly rs76481776 in MIR182 gene was associated with POAG after adjustment for multiple comparisons (odds ratio [OR] = 1.23, 95% confidence interval [CI]: 1.11–1.42, P = 0.0002). Subtype analysis indicated that the association was primarily in the HTG subset (OR = 1.26, 95% CI: 1.08–1.47, P = 0.004). The risk allele T has been associated with elevated miR-182 expression in vitro. Data from ddPCR and miRNA-Seq confirmed miR-182 expression in all examined ocular tissues and TM-derived exosomes. Interestingly, miR-182 expression in AH was 2-fold higher in HTG patients than nonglaucoma controls (P = 0.03) without controlling for medication treatment.ConclusionsOur integrative study is the first to associate rs76481776 with POAG via elevated miR-182 expression.

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Junb controls lymphatic vascular development in zebrafish via miR-182

Cited by 26 publications

References 66 publications

JunB regulates angiogenesis and neurovascular parallel alignment in mouse embryonic skin

JunB regulates angiogenesis and neurovascular parallel alignment in mouse embryonic skin

MicroRNA 199a-5p induces apoptosis by targeting JunB

A Common Variant in MIR182 Is Associated With Primary Open-Angle Glaucoma in the NEIGHBORHOOD Consortium

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