Endothelial Monocyte-Activating Polypeptide II Mediates Macrophage Migration in the Development of Hyperoxia-Induced Lung Disease of Prematurity

Lee, Daniel D.; Lal, Charitharth Vivek; Persad, Elizabeth; Lowe, Chinn Woan; Schwarz, Anna; Awasthi, Niranjan; Schwarz, Roderich E.; Schwarz, Margaret A.

doi:10.1165/rcmb.2016-0091oc

Cited by 21 publications

(20 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Animal harvesting. Overall techniques used in mouse lung harvesting and analysis have previously been published by our groups (16,22,(41)(42)(43). In brief, at P14, lungs were either inflation-fixed at 25 cm H 2 O with 4% paraformaldehyde for paraffin embedding/histology or were snap frozen for protein and RNA isolation.…”

Section: Methodsmentioning

confidence: 99%

“…In brief, at P14, lungs were either inflation-fixed at 25 cm H 2 O with 4% paraformaldehyde for paraffin embedding/histology or were snap frozen for protein and RNA isolation. BALF was obtained at P14 as previously described (22,41,42) and was used for exosome and cytokine analyses. All studies were performed with 4-9 animals per group, per condition, in every experiment.…”

Section: Methodsmentioning

confidence: 99%

“…In vivo mouse hyperoxia model. We utilized the well-established hyperoxia model of BPD (22,23). Exosomal miR 876-3p expression progressively decreased in BALF of hyperoxia-exposed pups on P4 (1 day after starting oxygen exposure), P7 (4 days after starting oxygen exposure), and P14 (on last day of oxygen exposure), compared with normoxia pups (all time points P < 0.05; Figure 4, A and B).…”

Section: Expression Of Mir-876-3p In Bpdmentioning

confidence: 99%

See 2 more Smart Citations

Exosomal microRNA predicts and protects against severe bronchopulmonary dysplasia in extremely premature infants

Lal

Olave²,

Travers³

et al. 2018

JCI Insight

View full text Add to dashboard Cite

Premature infants are at high risk for developing bronchopulmonary dysplasia (BPD), characterized by chronic inflammation and inhibition of lung development, which we have recently identified as being modulated by microRNAs (miRNAs) and alterations in the airway microbiome. Exosomes and exosomal miRNAs may regulate cell differentiation and tissue and organ development. We discovered that tracheal aspirates from infants with severe BPD had increased numbers of, but smaller, exosomes compared with term controls. Similarly, bronchoalveolar lavage fluid from hyperoxia-exposed mice (an animal model of BPD) and supernatants from hyperoxia-exposed human bronchial epithelial cells (in vitro model of BPD) had increased exosomes compared with air controls. Next, in a prospective cohort study of tracheal aspirates obtained at birth from extremely preterm infants, utilizing independent discovery and validation cohorts, we identified unbiased exosomal miRNA signatures predictive of severe BPD. The strongest signal of reduced miR-876-3p in BPD-susceptible compared with BPD-resistant infants was confirmed in the animal model and in vitro models of BPD. In addition, based on our recent discovery of increased Proteobacteria in the airway microbiome being associated with BPD, we developed potentially novel in vivo and in vitro models for BPD combining Proteobacterial LPS and hyperoxia exposure. Addition of LPS led to a larger reduction in exosomal miR 876-3p in both hyperoxia and normoxia compared with hyperoxia alone, thus indicating a potential mechanism by which alterations in microbiota can suppress miR 876-3p. Gain of function of miR 876-3p improved the alveolar architecture in the in vivo BPD model, demonstrating a causal link between miR 876-3p and BPD. In summary, we provide evidence for the strong predictive biomarker potential of miR 876-3p in severe BPD. We also provide insights on the pathogenesis of neonatal lung disease, as modulated by hyperoxia and microbial product-induced changes in exosomal miRNA 876-3p, which could be targeted for future therapeutic development.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Expression Of Mir-876-3p In Bpdmentioning

confidence: 99%

See 1 more Smart Citation

Exosomal microRNA predicts and protects against severe bronchopulmonary dysplasia in extremely premature infants

Lal

Olave²,

Travers³

et al. 2018

JCI Insight

View full text Add to dashboard Cite

show abstract

“…Abnormal lung vascular development is also a characteristic pathophysiologic feature of BPD (13), and higher concentrations of endostatin (an angiogenesis inhibitor) have been found in tracheal aspirates of infants with BPD (14,15). Animal studies show that hyperoxia decreases endothelial mitochondrial antioxidant defenses and disrupts pulmonary endothelial tight junctions, leading to arrested pulmonary development (16)(17)(18)(19)(20).…”

mentioning

confidence: 99%

Vascular Endothelial Mitochondrial Function Predicts Death or Pulmonary Outcomes in Preterm Infants

Kandasamy

Olave

Ballinger

et al. 2017

Am J Respir Crit Care Med

View full text Add to dashboard Cite

show abstract

“…At present, it has been found that EMAP-II has many functions on regulating cell function. In the development of hyperoxia-induced lung disease of prematurity, EMAP-II can mediate macrophage migration (Lee et al, 2016 ). EMAP-II is increased in children and adolescents with type I diabetes, which are related to micro-vascular complications (Adly et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

The Role of miR-330-3p/PKC-α Signaling Pathway in Low-Dose Endothelial-Monocyte Activating Polypeptide-II Increasing the Permeability of Blood-Tumor Barrier

Liu

Chao

et al. 2017

Front. Cell. Neurosci.

View full text Add to dashboard Cite

This study was performed to determine whether EMAP II increases the permeability of the blood-tumor barrier (BTB) by affecting the expression of miR-330-3p as well as its possible mechanisms. We determined the over-expression of miR-330-3p in glioma microvascular endothelial cells (GECs) by Real-time PCR. Endothelial monocyte-activating polypeptide-II (EMAP-II) significantly decreased the expression of miR-330-3p in GECs. Pre-miR-330-3p markedly decreased the permeability of BTB and increased the expression of tight junction (TJ) related proteins ZO-1, occludin and claudin-5, however, anti-miR-330-3p had the opposite effects. Anti-miR-330-3p could enhance the effect of EMAP-II on increasing the permeability of BTB, however, pre-miR-330-3p partly reversed the effect of EMAP-II on that. Similarly, anti-miR-330-3p improved the effects of EMAP-II on increasing the expression levels of PKC-α and p-PKC-α in GECs and pre-miR-330-3p partly reversed the effects. MiR-330-3p could target bind to the 3′UTR of PKC-α. The results of in vivo experiments were similar to those of in vitro experiments. These suggested that EMAP-II could increase the permeability of BTB through inhibiting miR-330-3p which target negative regulation of PKC-α. Pre-miR-330-3p and PKC-α inhibitor decreased the BTB permeability and up-regulated the expression levels of ZO-1, occludin and claudin-5 while anti-miR-330-3p and PKC-α activator brought the reverse effects. Compared with EMAP-II, anti-miR-330-3p and PKC-α activator alone, the combination of the three combinations significantly increased the BTB permeability. EMAP-II combined with anti-miR-330-3p and PKCα activator could enhance the DOX’s effects on inhibiting the cell viabilities and increasing the apoptosis of U87 glioma cells. Our studies suggest that low-dose EMAP-II up-regulates the expression of PKC-α and increases the activity of PKC-α by inhibiting the expression of miR-330-3p, reduces the expression of ZO-1, occludin and claudin-5, and thereby increasing the permeability of BTB. The results can provide a new strategy for the comprehensive treatment of glioma.

show abstract

Endothelial Monocyte-Activating Polypeptide II Mediates Macrophage Migration in the Development of Hyperoxia-Induced Lung Disease of Prematurity

Cited by 21 publications

References 49 publications

Exosomal microRNA predicts and protects against severe bronchopulmonary dysplasia in extremely premature infants

Exosomal microRNA predicts and protects against severe bronchopulmonary dysplasia in extremely premature infants

Vascular Endothelial Mitochondrial Function Predicts Death or Pulmonary Outcomes in Preterm Infants

The Role of miR-330-3p/PKC-α Signaling Pathway in Low-Dose Endothelial-Monocyte Activating Polypeptide-II Increasing the Permeability of Blood-Tumor Barrier

Contact Info

Product

Resources

About