&lt;p&gt;Effect of the Recombinant Adenovirus-Mediated HIF-1 Alpha on the Expression of VEGF in the Hypoxic Brain Microvascular Endothelial Cells of Rats&lt;/p&gt;

Jin, Ming-Lu; Zou, Zhehua; Tao, Tao; Li, Jun; Xu, Jian; Luo, Kai-Jian; Liu, Zhi

doi:10.2147/ndt.s238616

Cited by 15 publications

(21 citation statements)

References 49 publications

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“…At the protein level, HMGB1 protein increased in parallel with the mRNA also to 3.2 ± 0.1 − fold relative to aerobic cells, whereas HIF-1 protein under H/A was 1.8 ± 0.1 − fold of aerobic cells, a 50% decline relative to neutral hypoxia. As discussed in Methods, previous work by others and ourselves has shown that HIF-1 α accumulates rapidly when primary ECs are exposed to hypoxia, maximally within 4-8 h with no significant change between 24 and 72 h in most cases [ 56 , 57 , 61 ]. The results indicate positive regulation of all 3 RNA/gene targets by hypoxia and quenching of miR-126 and HIF-1 α by concurrent acidosis, but enhanced expression of HMGB1 by H/A.…”

Section: Resultsmentioning

confidence: 99%

MiR-126-HMGB1-HIF-1 Axis Regulates Endothelial Cell Inflammation during Exposure to Hypoxia-Acidosis

Liu

Wei²,

Wei

et al. 2021

Disease Markers

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Crosstalk between molecular regulators miR-126, hypoxia-inducible factor 1-alpha (HIF-1-α), and high-mobility group box-1 (HMGB1) contributes to the regulation of inflammation and angiogenesis in multiple physiological and pathophysiological settings. Here, we present evidence of an overriding role for miR-126 in the regulation of HMGB1 and its downstream proinflammatory effectors in endothelial cells subjected to hypoxia with concurrent acidosis (H/A). Methods. Primary mouse endothelial cells (PMEC) were exposed to hypoxia or H/A to simulate short or chronic low-flow ischemia, respectively. RT-qPCR quantified mRNA transcripts, and proteins were measured by western blot. ROS were quantified by fluorogenic ELISA and luciferase reporter assays employed to confirm an active miR-126 target in the HMGB1 3 ′ UTR. Results. Enhanced expression of miR-126 in PMECs cultured under neutral hypoxia was suppressed under H/A, whereas the HMGB1 expression increased sequentially under both conditions. Enhanced expression of HMGB1 and downstream inflammation markers was blocked by the premiR-126 overexpression and optimized by antagomiR. Compared with neutral hypoxia, H/A suppressed the HIF-1α expression independently of miR-126. The results show that HMGB1 and downstream effectors are optimally induced by H/A relative to neutral hypoxia via crosstalk between hypoxia signaling, miR-126, and HIF-1α, whereas B-cell lymphoma 2(Bcl2), a HIF-1α, and miR-126 regulated gene expressed optimally under neutral hypoxia. Conclusion. Inflammatory responses of ECs to H/A are dynamically regulated by the combined actions of hypoxia, miR-126, and HIF-1α on the master regulator HMGB1. The findings may be relevant to vascular diseases including atherosclerotic occlusion and interiors of plaque where coexisting hypoxia and acidosis promote inflammation as a defining etiology.

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Section: Resultsmentioning

confidence: 99%

MiR-126-HMGB1-HIF-1 Axis Regulates Endothelial Cell Inflammation during Exposure to Hypoxia-Acidosis

Liu

Wei²,

Wei

et al. 2021

Disease Markers

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“…In CNS microglia and astrocytes are two types of resident glial cells that communicating each other under homeostatic conditions and under affecting by pathology. 32 It has been reported that microglia in CNS do not express ERα. 28 The effect of TNA on microglial M2 polarization abolished by ICI, an estrogen receptors antagonist, is via blocking ERβ instead of via ERα.…”

Section: Discussionmentioning

confidence: 99%

“…RT-PCR was performed s describe before. 32 Following manufacturer’s instructions total RNA from lung or BV-2 cells was extracted by using RNeasy kits (Invitrogen, St. Louis, MO, USA). An on-column addition of DNase (Qiagen, Crawley, UK) was used to prevent DNA contamination according to manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

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Tanshinone IIA Promotes M2 Microglia by ERβ/IL-10 Pathway and Attenuates Neuronal Loss in Mouse TBI Model

Chen¹,

Chen²,

Tao

2020

NDT

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Purpose: Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. Increasing evidence indicates that activated microglia play an important role in the inflammatory response in TBI. Inhibiting M1 and stimulating M2 activated microglia have protective effects in several animal models of central nervous system (CNS) disorders. In the present study, we investigated whether tanshinone IIA (TNA) protects neurons by shifting microglia polarization in a mouse TBI model and further investigated the mechanism in vitro. Materials and Methods: Forty C57BL/6 mice were used to investigate the effect of TNA on microglia polarization in TBI. BV-2 cells were used to examine the mechanism of TNA in regulating microglia polarization. Results: Normal saline (NS), TNA and the combination of TNA with ICI 182,780 (ICI, an estrogen receptor antagonist) were used to treat the TBI mice. After TBI, mice from each group demonstrated functional improvement. The improvement rate in mice treated with TNA was faster than other groups. ICI partially reversed the benefits from TNA treatment. TNA treatment significantly reduced TBI-induced neuronal loss. The number of microglia after TBI was not significantly changed by TNA treatment. However, TNA treatment significantly decreased M1 macrophage markers (iNOS, TNFα and IL-1β) and increased M2 macrophage markers (CD206, arginase 1 and Ym1). This effect was partially abolished by ICI. TNA treatment downregulated M1 macrophage markers and upregulated M2 macrophage markers in BV-2 cells under LPS stimulation. IL-10 was significantly increased by TNA treatment without a significantly change of IL-4 and IL-13 expression. IL-10 knockdown completely abolished the effect of TNA on microglial M2 polarization. Conclusion:Taken together, our data demonstrated that TNA attenuates neuronal loss in mouse TBI model and promotes M2 microglia by ERβ/IL-10 pathway. Thus, TNA could be a potential drug for TBI and/or the disorders that caused by microglial over-activation in CNS.

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“…In a rat model of induced PE, HIF-1α level was found to increase with the onset of disease, show rapid elevation until 72 h in the untreated period, then increase at a slower rate until week 4 [13]. In another study of recombinant adenovirus-mediated HIF-1α in a rat model, it was observed that HIF-1α increased VEGF-A level, which plays an important role in thrombus organization and thrombolysis [14]. It was observed that HIF-1α, the main inducer of VEGF synthesis, also plays an important role in transmural angiogenesis in heart failure in addition to the effects of VEGF on thrombi [15].…”

Section: Discussionmentioning

confidence: 95%

Could HIF-1α be a novel biomarker for the clinical course and treatment of pulmonary embolism?

Kerget

Afşin²,

Aksakal

et al. 2020

Turk J Med Sci

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Background/aim: Pulmonary embolism (PE) is associated with high morbidity and mortality rates if not diagnosed and treated rapidly. The aim of our study was to investigate the relationship between levels of hypoxia-induced factor-1 alpha (HIF-1α) and clinical course and prognosis in patients with intermediate low-risk, intermediate high-risk, and high-risk PE. Materials and methods: The study included 240 subjects in 4 groups: a healthy control group (n = 60, mean age = 60 ± 15.2, female/male = 30/30), intermediate low-risk PE group (n = 60, mean age = 60 ± 12,5, female/male = 27/33), intermediate high-risk PE group (n = 60, mean age = 61,4 ± 14,8, female/male = 36/24), and high-risk PE group (n = 60, mean age = 62,3 ± 15, female/male = 33/27). Plasma HIF-1α levels were measured using commercial enzyme-linked immunosorbent assay (ELISA) kit. Results: Comparison of HIF-1α levels revealed a statistically significant difference between the groups in proportion to clinical scoring (P = 0.001 for all). Comparison of initial HIF-1α and troponin levels in intermediate high-risk PE patients given thrombolytic therapy and those treated with enoxaparin sodium showed that HIF-1α levels were significantly higher in the group that received thrombolytic therapy (P = 0.001), while there was no difference in troponin levels (P = 0.146). Conclusion: HIF-1α can be used in the PE clinical risk stratification and monitoring of PE and may also serve as a valuable early indicator in intermediate high-risk PE, for which early reperfusion therapy is important.

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<p>Effect of the Recombinant Adenovirus-Mediated HIF-1 Alpha on the Expression of VEGF in the Hypoxic Brain Microvascular Endothelial Cells of Rats</p>

Cited by 15 publications

References 49 publications

MiR-126-HMGB1-HIF-1 Axis Regulates Endothelial Cell Inflammation during Exposure to Hypoxia-Acidosis

MiR-126-HMGB1-HIF-1 Axis Regulates Endothelial Cell Inflammation during Exposure to Hypoxia-Acidosis

Tanshinone IIA Promotes M2 Microglia by ERβ/IL-10 Pathway and Attenuates Neuronal Loss in Mouse TBI Model

Could HIF-1α be a novel biomarker for the clinical course and treatment of pulmonary embolism?

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