Attribution of vascular phenotypes of the murine <i>Egfl7</i> locus to the microRNA <i>miR-126</i>

Kuhnert, Frank; Mancuso, Michael R.; Hampton, Jessica P.; Stankunas, Kryn; Asano, Tomohiko; Chen, Chang Zheng; Kuo, Calvin J.

doi:10.1242/dev.029736

Cited by 308 publications

(337 citation statements)

References 25 publications

Supporting

Mentioning

326

Contrasting

Unclassified

Order By: Relevance

“…Conditional deletion of VCAM1 or α4-integrin in hematopoietic, stromal and endothelial cells by a Tie2-driven cre transgene increased the release of hematopoietic progenitors from the bone marrow into the circulation. 37,38 Antibodies to VCAM1, to α4 integrin, 22,24,25 and BIO5192, a small molecule inhibitor of VLA4 (α4b1 integrin) binding to VCAM1, 21 promoted the mobilization of HSPC in mice and/or humans, providing strong evidence that disruption of an interaction between VLA4 and VCAM1 promotes HSPC mobilization. 37 However, a link between G-CSF mobilization of HSPC and modulation of VCAM1/VLA4 in the bone marrow has previously been missing.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA126 contributes to granulocyte colony-stimulating factor-induced hematopoietic progenitor cell mobilization by reducing the expression of vascular cell adhesion molecule 1

Salvucci

Jiang²,

Gasperini³

et al. 2012

Haematologica

View full text Add to dashboard Cite

The online version of this article has a Supplementary Appendix. BackgroundMobilization of hematopoietic stem/progenitor cells from the bone marrow to the peripheral blood by granulocyte colony-stimulating factor is the primary means to acquire stem cell grafts for hematopoietic cell transplantation. Since hematopoietic stem/progenitor cells represent a minority of all blood cells mobilized by granulocyte colony-stimulating factor, the underlying mechanisms need to be understood in order to develop selective drugs. Design and MethodsWe analyzed phenotypic, biochemical and genetic changes in bone marrow cell populations from granulocyte colony-stimulating factor-mobilized and control mice, and linked such changes to effective mobilization of hematopoietic stem/progenitor cells. ResultsWe show that granulocyte colony-stimulating factor indirectly reduces expression of surface vascular cell adhesion molecule 1 on bone marrow hematopoietic stem/progenitor cells, stromal cells and endothelial cells by promoting the accumulation of microRNA-126 (miR126)-containing microvescicles in the bone marrow extracellular compartment. We found that hematopoietic stem/progenitor cells, stromal cells and endothelial cells readily incorporate these miR126-loaded microvescicles, and that miR126 represses vascular cell adhesion molecule 1 expression on bone marrow hematopoietic stem/progenitor cells, stromal cells and endothelial cells. In line with this, miR126-null mice displayed a reduced mobilization response to granulocyte colony-stimulating factor. ConclusionsOur results implicate miR126 in the regulation of hematopoietic stem/progenitor cell trafficking between the bone marrow and peripheral sites, clarify the role of vascular cell adhesion molecule 1 in granulocyte colony-stimulating factor-mediated mobilization, and have important implications for improved approaches to selective mobilization of hematopoietic stem/progenitor cells.

show abstract

Section: Discussionmentioning

confidence: 99%

MicroRNA126 contributes to granulocyte colony-stimulating factor-induced hematopoietic progenitor cell mobilization by reducing the expression of vascular cell adhesion molecule 1

Salvucci

Jiang²,

Gasperini³

et al. 2012

Haematologica

View full text Add to dashboard Cite

show abstract

“…Some studies have also demonstrated that miR-126 has roles in regulating adhesion molecule expression (Harris et al, 2008), providing additional control of vascular inflammation (Harris et al, 2008), regulating the VEGF/PI3K/AKT signaling pathway (Hu et al, 2010), regulating the translation and invasiveness of vascular endothelial cell sprouting (Musiyenko et al, 2008), and governing the integrity and angiogenesis of the vasculature (Kuhnert et al, 2008;Wang et al, 2008b). Using MTT assays, our research showed that the SR of Siha-miR-126 mimic was significantly reduced compared to that of control cells and that the differences between the 2 cell groups increased over time.…”

Section: Discussionmentioning

confidence: 99%

miR-126 Suppresses the Proliferation of Cervical Cancer Cells and Alters Cell Sensitivity to the Chemotherapeutic Drug Bleomycin

Liu²,

Wang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

show abstract

“…Human Y79 retinoblastoma-derived cells (4 × 10 5 cells per well; ATCC) were transfected with Lipofectamine 2000 (Invitrogen) in 12-well plates with each of the six miRs from the miR-17 family. Distinct time points (3,6,12, and 24 h) as well as various miR concentrations (3, 10, and 30 nM) were tested to evaluate the effects of miR transfection on the levels of HIF1A and VEGFA expression relative to negative controls. Off-target effects and specificity of the selected miRs were further evaluated using the nontargeted, Cy5-labeled control 1 miR (Ambion) at the same time points and concentrations.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, a large body of literature identified and confirmed a number of miRs that regulate angiogenesis (1)(2)(3)(4)(5)(6)(7)(8).…”

mentioning

confidence: 99%

Synchronous down-modulation of miR-17 family members is an early causative event in the retinal angiogenic switch

Nunes

Dias-Neto

Cardó-Vila

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Six members of the microRNA-17 (miR-17) family were mapped to three different chromosomes, although they share the same seed sequence and are predicted to target common genes, among which are those encoding hypoxia-inducible factor-1α (HIF1A) and VEGFA. Here, we evaluated the in vivo expression profile of the miR-17 family in the murine retinopathy of prematurity (ROP) model, whereby Vegfa expression is highly enhanced at the early stage of retinal neovascularization, and we found simultaneous reduction of all miR-17 family members at this stage. Using gene reporter assays, we observed binding of these miRs to specific sites in the 3′ UTRs of Hif1a and Vegfa. Furthermore, overexpression of these miRs decreased HIF1A and VEGFA expression in vitro. Our data indicate that this miR-17 family elicits a regulatory synergistic down-regulation of Hif1a and Vegfa expression in this biological model. We propose the existence of a coordinated regulatory network, in which diverse miRs are synchronously regulated to target the Hif1a transcription factor, which in turn, potentiates and reinforces the regulatory effects of the miRs on Vegfa to trigger and sustain a significant physiological response. In humans, the miR-17 family is composed of six distinct mature miRs located on three chromosomes: miR-17-5p and miR-20a are located on chromosome 13q31.3, miR-20b and miR106a are located on chromosome Xq26.2, and miR-106b and miR-93 are located on chromosome 7q22.1. Members of this family seem to be derived from gene duplication events (9), and despite some divergences in length and nucleotide composition, their seed sequence (AAAGUG) is identical, an attribute suggestive of functional redundancy (10). Although the miR-17-92 cluster has been well-characterized, the regulatory role of the miR-17 family members has not been extensively studied (11,12). Distinct prediction algorithms (13-16) indicate that the miR-17 miR family may target the 3′ UTRs of genes encoding hypoxia-inducible factor-1α (HIF1A) and VEGFA. Therefore, by simultaneously targeting these two key genes, miR-17 family members could, in theory, be important concerted regulators of angiogenesis. As proof of concept, we tested this hypothesis in the experimental mouse model of retinopathy of prematurity (ROP), where Vegfa seems to be a pivotal factor that modulates the angiogenic switch (17)(18)(19). In this model, the expression of retinal Vegfa mRNA increases sharply 12 h after the animals are returned from 75% oxygen (O 2 ) back to room air (∼21% O 2 ), a process that induces a relative hypoxic condition and leads to retinal neovascularization in the subsequent 9 d (17-19).Here, we show the synchronous down-regulation of all members of the miR-17 family in the critical early steps of neovascularization in the ROP model. We propose an miR regulatory network, in which distinct and partially redundant miR-17 family members simultaneously affect the levels of the Hif1a transcription factor to posttranscriptionally (either directly and/or indirectly) increase the expres...

show abstract

Attribution of vascular phenotypes of the murine Egfl7 locus to the microRNA miR-126

Cited by 308 publications

References 25 publications

MicroRNA126 contributes to granulocyte colony-stimulating factor-induced hematopoietic progenitor cell mobilization by reducing the expression of vascular cell adhesion molecule 1

MicroRNA126 contributes to granulocyte colony-stimulating factor-induced hematopoietic progenitor cell mobilization by reducing the expression of vascular cell adhesion molecule 1

miR-126 Suppresses the Proliferation of Cervical Cancer Cells and Alters Cell Sensitivity to the Chemotherapeutic Drug Bleomycin

Synchronous down-modulation of miR-17 family members is an early causative event in the retinal angiogenic switch

Contact Info

Product

Resources

About