Biliverdin modulates the long non-coding RNA H19/microRNA-181b-5p/endothelial cell specific molecule 1 axis to alleviate cerebral ischemia reperfusion injury

Li, Junjie; Jiang, Haiyan; Peng, Pei-Hua; Zhang, Qi; Bai, Wenya; Yang, Yuan; Huo, Siying; Zhou, Guilin; Shao, Jianlin

doi:10.1016/j.biopha.2022.113455

Cited by 9 publications

(4 citation statements)

References 57 publications

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“…Therefore, reduced H19 expression in EVLdeficient mice may constitute an additional link to the observed vascular phenotype. Fitting with this hypothesis and the reduced Esm1 levels in EVL-deficient animals, impaired lncRNA H19 expression has recently been shown to downregulate Esm1 expression via reduced sponging of microRNA 181b-5p (Li et al, 2022). Esm1 in turn has been shown to enhance VEGF bioavailability and thereby increase retinal angiogenesis (Rocha et al, 2014), indicating that H19 deficiency reduces VEGF levels via Esm1.…”

Section: Resultsmentioning

confidence: 93%

Impaired H19 lncRNA expression contributes to the compromised developmental angiogenesis in EVL-deficient mice

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Froemel

Boon

et al. 2023

Preprint

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Endothelial tip cells are essential for VEGF-induced angiogenesis, but underlying mechanisms are elusive. Endothelial-specific deletion of EVL, a member of the mammalian Ena/VASP protein family, reduced the expression of the tip cell marker protein endothelial cell specific molecule-1 (Esm1) and compromised the radial sprouting of the vascular plexus in the postnatal mouse retina. The latter effects could at least partly be attributed to reduced VEGF receptor 2 (VEGFR2) internalization and signaling but the underlying mechanisms(s) are not fully understood. In the present study, we revealed that the expression of the long non-coding RNA H19 was significantly reduced in endothelial cells from postnatal EVL-/- mice and in siRNA-transfected human endothelial cells under hypoxic conditions. H19 was recently shown to promote VEGF expression and bioavailability via Esm1 and hypoxia inducible factor 1α (HIF-1α). Similar to EVL-/- mice, the radial outgrowth of the vascular plexus was significantly delayed in the postnatal retina of H19-/- mice. In summary, our data suggests that loss of EVL not only impairs VEGFR2 internalization and downstream signaling, but also impairs VEGF expression and bioavailability in the hypoxic retina via downregulation of lncRNA H19.

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Section: Resultsmentioning

confidence: 93%

Impaired H19 lncRNA expression contributes to the compromised developmental angiogenesis in EVL-deficient mice

Zink

Froemel

Boon

et al. 2023

Preprint

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“…But in human, BV have previously been considered to act as a natural antioxidant [21], protecting lipids from reactive oxygen species (ROS) as part of the biliverdin-bilirubin cycle [22]. At present, some studies have reported the beneficial effects of BV in biomedicine, such as reducing ischemia reperfusion injury of multiple organs [23,24], inhibiting endotoxin-induced inflammatory response [25], and suppressing Porcine reproductive and respiratory syndrome (PRRSV) infection [26]. However, BV has also been investigated as a specific plasma metabolite biomarker in male patients with major depressive disorder [27].…”

Section: Discussionmentioning

confidence: 99%

Enterococcus faecalis promotes the progression of colorectal cancer via its metabolite: biliverdin

et al. 2023

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Background Enterococcus faecalis (Efa) has been shown to be a “driver bacteria” in the occurrence and development of colorectal cancer (CRC). This study aims to explore the effect of specific metabolites of Efa on CRC. Methods The pro-tumor effects of Efa were assessed in colonic epithelial cells. The tumor-stimulating molecule produced by Efa was identified using liquid chromatography mass spectrometry (LC-MS). The proliferative effect of metabolites on CRC cells in vitro was assayed as well. The concentration of vascular endothelial growth factor A (VEGFA) and interleukin-8 (IL-8) was determined using enzyme-linked immunosorbent assay (ELISA). Tubular formation assay of human umbilical vein endothelial cells (HUVEC) and cell migration assay were applied to study angiogenesis. Additionally, western blot analysis was used to investigate key regulatory proteins involved in the angiogenesis pathway. Tumor growth was assessed using mouse models with two CRC cells and human colon cancer organoid. Results Co-incubation with the conditioned medium of Efa increased the proliferation of cultured CRC cells. Biliverdin (BV) was determined as the key metabolite produced by Efa using LC-MS screening. BV promoted colony formation and cell proliferation and inhibited cell cycle arrest of cultured CRC cells. BV significantly increased the expression level of IL-8 and VEGFA by regulating the PI3K/AKT/mTOR signaling pathway, leading to the acceleration of angiogenesis in CRC. The up-regulation of proliferation and angiogenesis by BV were also confirmed in mice. Conclusion In conclusion, BV, as the tumor-stimulating metabolite of Efa, generates proliferative and angiogenic effects on CRC, which is mainly mediated by the activation of PI3K/AKT/mTOR.

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“…BV could effectively diminish the upregulation of proinflammatory mediators such as IL-6, CCL2, and iNOS and relieve lipid peroxidation, giving rise to a reduction in intestinal mucosal injury in an in vivo intestinal transplantation model [ 91 ]. BV also inhibits cerebral ischemia reperfusion-induced cell apoptosis and ameliorates cerebral ischemia reperfusion injury (CIR) in the rat cortex by downregulating lncRNA H19 [ 92 ]. Another investigation proposed that elevated miRNA204-5p expression and its direct interaction with Ets1 was the underlying mechanism of BV-related neural improvement [ 93 ].…”

Section: Biological Functions Of Ho-1mentioning

confidence: 99%

Cytoprotective Role of Heme Oxygenase-1 in Cancer Chemoresistance: Focus on Antioxidant, Antiapoptotic, and Pro-Autophagy Properties

et al. 2023

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Chemoresistance remains the foremost challenge in cancer therapy. Targeting reactive oxygen species (ROS) manipulation is a promising strategy in cancer treatment since tumor cells present high levels of intracellular ROS, which makes them more vulnerable to further ROS elevation than normal cells. Nevertheless, dynamic redox evolution and adaptation of tumor cells are capable of counteracting therapy-induced oxidative stress, which leads to chemoresistance. Hence, exploring the cytoprotective mechanisms of tumor cells is urgently needed to overcome chemoresistance. Heme oxygenase-1 (HO-1), a rate-limiting enzyme of heme degradation, acts as a crucial antioxidant defense and cytoprotective molecule in response to cellular stress. Recently, emerging evidence indicated that ROS detoxification and oxidative stress tolerance owing to the antioxidant function of HO-1 contribute to chemoresistance in various cancers. Enhanced HO-1 expression or enzymatic activity was revealed to promote apoptosis resistance and activate protective autophagy, which also involved in the development of chemoresistance. Moreover, inhibition of HO-1 in multiple cancers was identified to reversing chemoresistance or improving chemosensitivity. Here, we summarize the most recent advances regarding the antioxidant, antiapoptotic, and pro-autophagy properties of HO-1 in mediating chemoresistance, highlighting HO-1 as a novel target for overcoming chemoresistance and improving the prognosis of cancer patients.

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Biliverdin modulates the long non-coding RNA H19/microRNA-181b-5p/endothelial cell specific molecule 1 axis to alleviate cerebral ischemia reperfusion injury

Cited by 9 publications

References 57 publications

Impaired H19 lncRNA expression contributes to the compromised developmental angiogenesis in EVL-deficient mice

Impaired H19 lncRNA expression contributes to the compromised developmental angiogenesis in EVL-deficient mice

Enterococcus faecalis promotes the progression of colorectal cancer via its metabolite: biliverdin

Cytoprotective Role of Heme Oxygenase-1 in Cancer Chemoresistance: Focus on Antioxidant, Antiapoptotic, and Pro-Autophagy Properties

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