Celastrol inhibits pathologic neovascularization in oxygen-induced retinopathy by targeting the miR-17-5p/HIF-1α/VEGF pathway

Zhao, Kun; Jiang, Yaping; Zhang, Jing; Shi, Jing; Zheng, Pengxiang; Yang, Chuanxi; Chen, Yihui

doi:10.1080/15384101.2022.2087277

Cited by 14 publications

(9 citation statements)

References 63 publications

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“…The deletion of CCN1, a gene that encodes the extracellular matrixassociated integrin-binding protein, exacerbates the pro-inflammatory responses of microglia and leads to the malformation of retinal vasculature in the OIR model (Yan et al, 2015). And the administration 10.3389/fnmol.2023.1100254 Frontiers in Molecular Neuroscience frontiersin.org of Celastrol reverses the activation of the miR-17-5p/HIF-1α/VEGF signaling pathway which reduces retinal neovascularization by inhibiting the microglial activation and inflammation; the proliferation, migration and tube formation ability of human retinal microvascular endothelial cells are also inhibited in vitro culture (Zhao et al, 2022). In addition, KC7F2, a novel molecular compound, reduces retinal angiogenesis by reducing the co-localization ratio between microglia and neovascularization and inhibits the activation of the HIF1α/VEGF signaling pathway in human umbilical vein endothelial cells (Tang X. et al, 2022).…”

Section: Microglia In Oxygen-induced Retinopathy (Oir)mentioning

confidence: 99%

Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy

Feng

Qin

et al. 2023

Front. Mol. Neurosci.

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Microglia are the primary resident retinal macrophages that monitor neuronal activity in real-time and facilitate angiogenesis during retinal development. In certain retinal diseases, the activated microglia promote retinal angiogenesis in hypoxia stress through neurovascular coupling and guide neovascularization to avascular areas (e.g., the outer nuclear layer and macula lutea). Furthermore, continuously activated microglia secrete inflammatory factors and expedite the loss of the blood-retinal barrier which causes irreversible damage to the secondary death of neurons. In this review, we support microglia can be a potential cellular therapeutic target in retinopathy. We briefly describe the relevance of microglia to the retinal vasculature and blood-retinal barrier. Then we discuss the signaling pathway related to how microglia move to their destinations and regulate vascular regeneration. We summarize the properties of microglia in different retinal disease models and propose that reducing the number of pro-inflammatory microglial death and conversing microglial phenotypes from pro-inflammatory to anti-inflammatory are feasible for treating retinal neovascularization and the damaged blood-retinal barrier (BRB). Finally, we suppose that the unique properties of microglia may aid in the vascularization of retinal organoids.

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Section: Microglia In Oxygen-induced Retinopathy (Oir)mentioning

confidence: 99%

Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy

Feng

Qin

et al. 2023

Front. Mol. Neurosci.

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“…Natural products ( 116 Furthermore, sucurbitacin B inhibits proliferation and triggers apoptosis of gefitinib-resistant lung cancer cells by upregulating miR-17-5p. 117 Resveratrol suppresses LPS-triggered injury in keratinocytes by upregulating miR-17-5p.…”

Section: Mir-17-5pmentioning

confidence: 99%

“…Hypoxia induces angiogenesis in cultured human retinal microvascular endothelial cells (HRMEC) by downregulating miR‐17‐5p. Celastrol suppresses vascular endothelial growth factor (VEGF)‐promoted proliferation and migration, and inhibits hypoxia‐triggered angiogenesis in HRMEC cells by upregulating miR‐17‐5p 116 . Furthermore, sucurbitacin B inhibits proliferation and triggers apoptosis of gefitinib‐resistant lung cancer cells by upregulating miR‐17‐5p 117 .…”

Section: Connections Of Pp2a‐modulating Mirnas To Pp2a‐modulating Nat...mentioning

confidence: 99%

“…For PP2A‐activating natural products, carnosic acid upregulates miR‐19b‐3p and miR‐221‐3p, 126 and miR‐29b‐3p 138 and downregulates miR‐34a‐5p 145 . Celastrol upregulates miR‐17‐5p 116 and downregulates miR‐21‐5p 133 and miR‐345‐5p 142 . EGCG upregulates let‐7b‐5p, 23 miR‐1246 and miR‐21‐5p, 102 miR‐155‐5p, 110 and miR‐9‐5p 96 .…”

Section: Connections Of Pp2a‐modulating Mirnas To Pp2a‐modulating Nat...mentioning

confidence: 99%

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Protein phosphatase 2A modulation and connection with miRNAs and natural products

Chuang,

Yen,

Tang

et al. 2024

Environmental Toxicology

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Protein phosphatase 2A (PP2A), a heterotrimeric holoenzyme (scaffolding, catalytic, and regulatory subunits), regulates dephosphorylation for more than half of serine/threonine phosphosites and exhibits diverse cellular functions. Although several studies on natural products and miRNAs have emphasized their impacts on PP2A regulation, their connections lack systemic organization. Moreover, only part of the PP2A family has been investigated. This review focuses on the PP2A‐modulating effects of natural products and miRNAs' interactions with potential PP2A targets in cancer and non‐cancer cells. PP2A‐modulating natural products and miRNAs were retrieved through a literature search. Utilizing the miRDB database, potential PP2A targets of these PP2A‐modulating miRNAs for the whole set (17 members) of the PP2A family were retrieved. Finally, PP2A‐modulating natural products and miRNAs were linked via a literature search. This review provides systemic directions for assessing natural products and miRNAs relating to the PP2A‐modulating functions in cancer and disease treatments.

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“…These were then sorted by the number of target proteins (counts) in the pathways to screen the top 40 pathways (Figure S1B). Based on the literature, we found that the HIF-1, 34 TNF, 35 PI3K/AKT, 36 IL-17, 37 VEGF, 37 and JAK/STAT signaling pathways 38,39 were involved in the regulation of microgliamediated inflammatory responses. Accordingly, we initially selected these six signaling pathways for further study.…”

Section: Alpinetin Reduced the Levels Of Proinflammatory Cytokines In...mentioning

confidence: 99%

Alpinetin inhibits neuroinflammation and neuronal apoptosis via targeting the JAK2/STAT3 signaling pathway in spinal cord injury

et al. 2023

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Background A growing body of research shows that drug monomers from traditional Chinese herbal medicines have antineuroinflammatory and neuroprotective effects that can significantly improve the recovery of motor function after spinal cord injury (SCI). Here, we explore the role and molecular mechanisms of Alpinetin on activating microglia‐mediated neuroinflammation and neuronal apoptosis after SCI. Methods Stimulation of microglia with lipopolysaccharide (LPS) to simulate neuroinflammation models in vitro, the effect of Alpinetin on the release of pro‐inflammatory mediators in LPS‐induced microglia and its mechanism were detected. In addition, a co‐culture system of microglia and neuronal cells was constructed to assess the effect of Alpinetin on activating microglia‐mediated neuronal apoptosis. Finally, rat spinal cord injury models were used to study the effects on inflammation, neuronal apoptosis, axonal regeneration, and motor function recovery in Alpinetin. Results Alpinetin inhibits microglia‐mediated neuroinflammation and activity of the JAK2/STAT3 pathway. Alpinetin can also reverse activated microglia‐mediated reactive oxygen species (ROS) production and decrease of mitochondrial membrane potential (MMP) in PC12 neuronal cells. In addition, in vivo Alpinetin significantly inhibits the inflammatory response and neuronal apoptosis, improves axonal regeneration, and recovery of motor function. Conclusion Alpinetin can be used to treat neurodegenerative diseases and is a novel drug candidate for the treatment of microglia‐mediated neuroinflammation.

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Celastrol inhibits pathologic neovascularization in oxygen-induced retinopathy by targeting the miR-17-5p/HIF-1α/VEGF pathway

Cited by 14 publications

References 63 publications

Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy

Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy

Protein phosphatase 2A modulation and connection with miRNAs and natural products

Alpinetin inhibits neuroinflammation and neuronal apoptosis via targeting the JAK2/STAT3 signaling pathway in spinal cord injury

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