Novel Regulators of Retina Neovascularization: A Proteomics Approach

Xu, Manhong; Jiang, Yilin; Su, Lin; Chen, Xin; Shao, Xinyi; Ea, Vicki; Shang, Zhenying; Zhang, Xiao Min; Barnstable, Colin J.; Li, Xiaorong; Tombran-Tink, Joyce

doi:10.1021/acs.jproteome.1c00547

Cited by 10 publications

(5 citation statements)

References 79 publications

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“… 40 ECH1, an enzyme involved in fatty acid oxidation, was identified as an activator of NV using a proteomics approach in the murine OIR model and validated as highly up-regulated in hypoxic human retinal endothelial cells. 41 However, our findings that EMP2 blockade increases Acat1 and Ech1 expression, not decreases them, may contribute to the incomplete attenuation of neovascularization observed in our study. Last, peroxisome proliferator-activated receptor gamma (Pparγ) is upregulated by EMP2 blockade.…”

Section: Discussioncontrasting

confidence: 61%

Epithelial Membrane Protein 2 (EMP2) Blockade Attenuates Pathological Neovascularization in Murine Oxygen-Induced Retinopathy

Aguirre,

Lin,

Araujo

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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Section: Discussioncontrasting

confidence: 61%

Epithelial Membrane Protein 2 (EMP2) Blockade Attenuates Pathological Neovascularization in Murine Oxygen-Induced Retinopathy

Aguirre,

Lin,

Araujo

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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“…Investigator identified a set of proteins that may be integral to the OIR retina vascular remodeling process by using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). [ 42 ] The specific mechanisms on how SHED‐apoVs affect downstream vascular remodeling protein expression through PD1/PDL1 in different stages to improve retinal structure and function remains to be further explored.…”

Section: Discussionmentioning

confidence: 99%

Apoptotic Vesicles Modulate Endothelial Metabolism and Ameliorate Ischemic Retinopathy via PD1/PDL1 Axis

Jing,

Zhao,

Zhou

et al. 2024

Adv Healthcare Materials

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Pathological angiogenesis with subsequent disturbed microvascular remodeling is a major cause of irreversible blindness in a number of ischemic retinal diseases. The current anti‐VEGF therapy can effectively inhibit angiogenesis, but it also brings significant side effects. The emergence of stem cell derived extracellular vesicles provides a new underlining strategy for ischemic retinopathy. We extracted apoptotic vesicles (apoVs) from stem cells from human exfoliated deciduous teeth (SHED). SHED‐apoVs were delivered into the eyeballs of oxygen induced retinopathy (OIR, a most common model of angiogenic retinal dieseases) mice through intravitreal injection. The retinal neovascularization and non‐perfusion area, vascular structure, and density changes were observed during the neovascularization phase (P17) and vascular remodeling phase (P21), and visual function was measured. The expression of ECAR and lactic acid testing were used to detect endothelial cells (ECs) glycolytic activity. Furthermore, we used lentivirus and neutralizing antibody to block PD1‐PDL1 axis, investigating the effects of SHED‐apoVs on glycolysis and angiogenic activities. Our work showed that SHED‐apoVs were taken up by ECs and modulated the ECs glycolysis, leading to the decrease of abnormal neovessels and vascular remodeling. Furthermore, we found that, at the molecular level, apoVs‐carried PD1 interacted with PDL1 on hypoxic ECs to regulate the angiogenic activation. SHED‐apoVs inhibited pathological angiogenesis and promoted vascular remodeling in ischemic retinopathy partially by modulating ECs glycolysis through PD1/PDL1 axis. Our study provides a new potential strategy for the clinical treatment of pathological retinal neovascularization .This article is protected by copyright. All rights reserved

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“…reported that CD109 was among the most down-regulated proteins in hypoxic retinal endothelial cells. Overexpression of CD109 decreased, while downregulation increased endothelial cell proliferation in both human retinal and umbilical vein endothelial cells [ 75 ]. CD109 is a GPI-anchored protein that acts as a TGF-β co-receptor and a negative regulator of TGF-β signaling.…”

Section: Discussionmentioning

confidence: 99%

Loss of microRNA-30a and sex-specific effects on the neonatal hyperoxic lung injury

et al. 2023

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Background Bronchopulmonary dysplasia (BPD) is characterized by an arrest in lung development and is a leading cause of morbidity in premature neonates. It has been well documented that BPD disproportionally affects males compared to females, but the molecular mechanisms behind this sex-dependent bias remain unclear. Female mice show greater preservation of alveolarization and angiogenesis when exposed to hyperoxia, accompanied by increased miR-30a expression. In this investigation, we tested the hypothesis that loss of miR-30a would result in male and female mice experiencing similar impairments in alveolarization and angiogenesis under hyperoxic conditions. Methods Wild-type and miR-30a−/− neonatal mice were exposed to hyperoxia [95% FiO2, postnatal day [PND1-5] or room air before being euthanized on PND21. Alveolarization, pulmonary microvascular development, differences in lung transcriptome, and miR-30a expression were assessed in lungs from WT and miR-30a−/− mice of either sex. Blood transcriptomic signatures from preterm newborns (with and without BPD) were correlated with WT and miR-30a−/− male and female lung transcriptome data. Results Significantly, the sex-specific differences observed in WT mice were abrogated in the miR-30a−/− mice upon exposure to hyperoxia. The loss of miR-30a expression eliminated the protective effect in females, suggesting that miR-30a plays an essential role in regulating alveolarization and angiogenesis. Transcriptome analysis by whole lung RNA-Seq revealed a significant response in the miR-30a−/− female hyperoxia-exposed lung, with enrichment of pathways related to cell cycle and neuroactive ligand–receptor interaction. Gene expression signature in the miR-30a−/− female lung associated with human BPD blood transcriptomes. Finally, we showed the spatial localization of miR-30a transcripts in the bronchiolar epithelium. Conclusions miR-30a could be one of the biological factors mediating the resilience of the female preterm lung to neonatal hyperoxic lung injury. A better understanding of the effects of miR-30a on pulmonary angiogenesis and alveolarization may lead to novel therapeutics for treating BPD.

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Novel Regulators of Retina Neovascularization: A Proteomics Approach

Cited by 10 publications

References 79 publications

Epithelial Membrane Protein 2 (EMP2) Blockade Attenuates Pathological Neovascularization in Murine Oxygen-Induced Retinopathy

Epithelial Membrane Protein 2 (EMP2) Blockade Attenuates Pathological Neovascularization in Murine Oxygen-Induced Retinopathy

Apoptotic Vesicles Modulate Endothelial Metabolism and Ameliorate Ischemic Retinopathy via PD1/PDL1 Axis

Loss of microRNA-30a and sex-specific effects on the neonatal hyperoxic lung injury

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