Carbon monoxide prevents TNF-α-induced eNOS downregulation by inhibiting NF-κB-responsive miR-155-5p biogenesis

Choi, Seunghwan; Kim, Joohwan; Kim, Jihee; Lee, Dong Hoon; Park, Wonjin; Park, Minsik; Kim, Su-Ji; Hwang, Jong Yun; Won, Moo Ho; Choi, Yoon Kyung; Ryoo, Sungwoo; Ha, Kwon‐Soo; Kwon, Young Guen; Kim, Young Myeong

doi:10.1038/emm.2017.193

Cited by 45 publications

(38 citation statements)

References 54 publications

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“…However, inflammatory stimuli, such as TNF␣ and LPS, down-regulate the expression of this enzyme without transcriptional alteration through activation of NF-B (7). In addition, it has been shown that inhibition of the NF-B pathway can rescue decreased eNOS expression by preventing destabilization of eNOS mRNA under inflammatory conditions (3)(4)(5)(6)(7). This suggests that eNOS is negatively regulated in an NF-B-dependent manner at the post-transcriptional level.…”

Section: Endothelial Dysfunction By Mir-31-5pmentioning

confidence: 99%

“…The inflammatory response is finely controlled by transcription factors, including NF-B (NF-B), to prevent tissue or organ injury; however, prolonged and persistent activation of NF-B evokes elevated production of cytokines, such as tumor necrosis factor-␣ (TNF␣) and the interleukin (IL) family, which are important risk factors for several human diseases, including cardiovascular disorders and preeclampsia (2,3), although anti-angiogenic factors, hypoxia, and reactive oxygen species are also involved in the pathogenesis of these diseases (4). Chronic inflammation elicits functional alterations in vascular endothelial cells, which play a key role in regulating vascular relaxation and homeostasis (3,5). Studies have demonstrated that miRNA biogenesis is stimulated under inflammatory conditions and causes endothelial cell dysfunction, indicating that some miRNAs are risk factors in the pathogenesis of vascular diseases (2,3,5).…”

mentioning

confidence: 99%

“…Chronic inflammation elicits functional alterations in vascular endothelial cells, which play a key role in regulating vascular relaxation and homeostasis (3,5). Studies have demonstrated that miRNA biogenesis is stimulated under inflammatory conditions and causes endothelial cell dysfunction, indicating that some miRNAs are risk factors in the pathogenesis of vascular diseases (2,3,5).…”

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confidence: 99%

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NF-κB–responsive miRNA-31-5p elicits endothelial dysfunction associated with preeclampsia via down-regulation of endothelial nitric-oxide synthase

Kim

Lee

Choi

et al. 2018

Journal of Biological Chemistry

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Inflammatory cytokines, including tumor necrosis factor-␣ (TNF␣), were elevated in patients with cardiovascular diseases and are also considered as crucial factors in the pathogenesis of preeclampsia; however, the underlying pathogenic mechanism has not been clearly elucidated. This study provides novel evidence that TNF␣ leads to endothelial dysfunction associated with hypertension and vascular remodeling in preeclampsia through down-regulation of endothelial nitric-oxide synthase (eNOS) by NF-Bdependent biogenesis of microRNA (miR)-31-5p, which targets eNOS mRNA. In this study, we found that miR-31-5p was up-regulated in sera from patients with preeclampsia and in human endothelial cells treated with TNF␣. TNF␣-mediated induction of miR-31-5p was blocked by an NF-B inhibitor and NF-B p65 knockdown but not by mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase inhibitors, indicating that NF-B is essential for biogenesis of miR-31-5p. The treatment of human endothelial cells with TNF␣ or miR-31-5p mimics decreased endothelial nitricoxide synthase (eNOS) mRNA stability without affecting eNOS promoter activity, resulting in inhibition of eNOS expression and NO/cGMP production through blocking of the functional activity of the eNOS mRNA 3-UTR. Moreover, TNF␣ and miR-31-5p mimic evoked endothelial dysfunction associated with defects in angiogenesis, trophoblastic invasion, and vasorelaxation in an ex vivo cultured model of human placental arterial vessels, which are typical features of preeclampsia. These results suggest that NF-B-responsive miR-31-5p elicits endothelial dysfunction, hypertension, and vascular remodeling via posttranscriptional down-regulation of eNOS and is a molecular risk factor in the pathogenesis and development of preeclampsia.

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Section: Endothelial Dysfunction By Mir-31-5pmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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NF-κB–responsive miRNA-31-5p elicits endothelial dysfunction associated with preeclampsia via down-regulation of endothelial nitric-oxide synthase

Kim

Lee

Choi

et al. 2018

Journal of Biological Chemistry

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“…Cell and tissue debris was removed by centrifugation at 12,000 ϫ g for 15 min. Lysates (30 g of protein) were separated by SDS-PAGE, and target protein levels were determined by Western blot analysis (49).…”

Section: Western Blot Analysismentioning

confidence: 99%

TNF-α elicits phenotypic and functional alterations of vascular smooth muscle cells by miR-155-5p–dependent down-regulation of cGMP-dependent kinase 1

Choi

Park

Kim

et al. 2018

Journal of Biological Chemistry

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cGMP-dependent protein kinase 1 (PKG1) plays an important role in nitric oxide (NO)/cGMP-mediated maintenance of vascular smooth muscle cell (VSMC) phenotype and vasorelaxation. Inflammatory cytokines, including tumor necrosis factor-α (TNFα), have long been understood to mediate several inflammatory vascular diseases. However, the underlying mechanism of TNFα-dependent inflammatory vascular disease is unclear. Here, we found that TNFα treatment decreased PKG1 expression in cultured VSMCs, which correlated with NF-κB-dependent biogenesis of miR-155-5p that targeted the 3'-UTR of PKG1 mRNA. TNFα induced VSMC phenotypic switching from a contractile to a synthetic state through the down-regulation of VSMC marker genes, suppression of actin polymerization, alteration of cell morphology, and elevation of cell proliferation and migration. All of these events were blocked by treatment with an inhibitor of miR-155-5p or PKG1, whereas transfection with miR-155-5p mimic or PKG1 siRNA promoted phenotypic modulation, similar to the response to TNFα. In addition, TNFα-induced miR-155-5p inhibited the vasorelaxant response of de-endothelialized mouse aortic vessels to 8-Br-cGMP by suppressing phosphorylation of myosin phosphatase and myosin light chain, both of which are downstream signal modulators of PKG1. Moreover, TNFα-induced VSMC phenotypic alteration and vasodilatory dysfunction were blocked by NF-κB inhibition. These results suggest that TNFα impairs NO/cGMP-mediated maintenance of the VSMC contractile phenotype and vascular relaxation by down-regulating PKG1 through NF-κB-dependent biogenesis of miR-155-5p. Thus, the NF-κB/miR-155-5p/PKG1 axis may be crucial in the pathogenesis of inflammatory vascular diseases, such as atherosclerotic intimal hyperplasia and preeclamptic hypertension.

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“…NO and CO are endogenous gases produced by NOS and HO and they are freely diffusible through the cell membrane and possess neurogenic and angiogenic functions [10,152]. NO is produced by the reaction of L-arginine with NOS isoforms.…”

Section: Nitric Oxide (No)mentioning

confidence: 99%

Regenerative Potential of Carbon Monoxide in Adult Neural Circuits of the Central Nervous System

Jung

Koh

Yoo

et al. 2020

IJMS

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Regeneration of adult neural circuits after an injury is limited in the central nervous system (CNS). Heme oxygenase (HO) is an enzyme that produces HO metabolites, such as carbon monoxide (CO), biliverdin and iron by heme degradation. CO may act as a biological signal transduction effector in CNS regeneration by stimulating neuronal intrinsic and extrinsic mechanisms as well as mitochondrial biogenesis. CO may give directions by which the injured neurovascular system switches into regeneration mode by stimulating endogenous neural stem cells and endothelial cells to produce neurons and vessels capable of replacing injured neurons and vessels in the CNS. The present review discusses the regenerative potential of CO in acute and chronic neuroinflammatory diseases of the CNS, such as stroke, traumatic brain injury, multiple sclerosis and Alzheimer’s disease and the role of signaling pathways and neurotrophic factors. CO-mediated facilitation of cellular communications may boost regeneration, consequently forming functional adult neural circuits in CNS injury.

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Carbon monoxide prevents TNF-α-induced eNOS downregulation by inhibiting NF-κB-responsive miR-155-5p biogenesis

Cited by 45 publications

References 54 publications

NF-κB–responsive miRNA-31-5p elicits endothelial dysfunction associated with preeclampsia via down-regulation of endothelial nitric-oxide synthase

NF-κB–responsive miRNA-31-5p elicits endothelial dysfunction associated with preeclampsia via down-regulation of endothelial nitric-oxide synthase

TNF-α elicits phenotypic and functional alterations of vascular smooth muscle cells by miR-155-5p–dependent down-regulation of cGMP-dependent kinase 1

Regenerative Potential of Carbon Monoxide in Adult Neural Circuits of the Central Nervous System

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