Downregulation of Quinone Reductase 2 Attenuates Vascular Smooth Muscle Cells Proliferation and Neointimal Formation in Balloon Injured Rat Carotid Artery

Zhang, Xiwen; Wang, Yao; Cai, Jingbo; Hou, Xiaofeng; Wang, Hegui; Zou, Jiangang; Cao, Ke

doi:10.1159/000338499

Cited by 4 publications

(5 citation statements)

References 30 publications

(39 reference statements)

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“…The role of melatonin as an efficient ROS scavenger is well documented, and according to our data, melatonin may control redox homeostasis by regulating the expression of the NQO2 enzyme which is also a melatonin cytosolic receptor (MT3) 82 . Its antiproliferative effect in response to melatonin was observed in tumour cells such as HepG2 cells 83 ; however, it maintained the proliferation of vascular smooth muscle cells through ERK1/2 phosphorylation 84 .…”

Section: Discussionmentioning

confidence: 98%

The genomic response of human granulosa cells (KGN) to melatonin and specific agonists/antagonists to the melatonin receptors

Arjoune

Sirard

2022

Sci Rep

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Melatonin is a known modulator of follicle development; it acts through several molecular cascades via binding to its two specific receptors MT1 and MT2. Even though it is believed that melatonin can modulate granulosa cell (GC) functions, there is still limited knowledge of how it can act in human GC through MT1 and MT2 and which one is more implicated in the effects of melatonin on the metabolic processes in the dominant follicle. To better characterize the roles of these receptors on the effects of melatonin on follicular development, human granulosa-like tumor cells (KGN) were treated with specific melatonin receptor agonists and antagonists, and gene expression was analyzed with RNA-seq technology. Following appropriate normalization and the application of a fold change cut-off of 1.5 (FC 1.5, p ≤ 0.05) for each treatment, lists of the principal differentially expressed genes (DEGs) are generated. Analysis of major upstream regulators suggested that the MT1 receptor may be involved in the melatonin antiproliferative effect by reprogramming the metabolism of human GC by activating the PKB signaling pathway. Our data suggest that melatonin may act complementary through both MT1 and MT2 receptors to modulate human GC steroidogenesis, proliferation, and differentiation. However, MT2 receptors may be the ones implicated in transducing the effects of melatonin on the prevention of GC luteinization and follicle atresia at the antral follicular stage through stimulating the PKA pathway.

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Section: Discussionmentioning

confidence: 98%

The genomic response of human granulosa cells (KGN) to melatonin and specific agonists/antagonists to the melatonin receptors

Arjoune

Sirard

2022

Sci Rep

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“…The initial Northern blot findings in human specimens indicated that the highest expression was in skeletal muscle followed by kidneys, liver, lungs, and heart 54 , 55 . In previous studies using an NQO2 knockdown cell line and NQO2 siRNA, the inhibition of NQO2 activity induced the upregulation of antioxidant enzymes, which resulted in increased cellular resistance to oxidants and protected cellular components from oxidation-related damage 56 – 58 . Furthermore, high concentrations of resveratrol, which is a natural antioxidant agent, induced the downregulation of NQO2 expression, which inhibited the angiotensin II-induced generation of reactive species oxygens in rat vascular smooth muscle cells 57 , 58 .…”

Section: Discussionmentioning

confidence: 99%

“…In previous studies using an NQO2 knockdown cell line and NQO2 siRNA, the inhibition of NQO2 activity induced the upregulation of antioxidant enzymes, which resulted in increased cellular resistance to oxidants and protected cellular components from oxidation-related damage 56 – 58 . Furthermore, high concentrations of resveratrol, which is a natural antioxidant agent, induced the downregulation of NQO2 expression, which inhibited the angiotensin II-induced generation of reactive species oxygens in rat vascular smooth muscle cells 57 , 58 . An immunohistochemical toxicity study showed that TAA significantly reduced the expression level of NQO1 in rat renal tissues 59 .…”

Section: Discussionmentioning

confidence: 99%

Nephrotoxicity evaluation and proteomic analysis in kidneys of rats exposed to thioacetamide

Lim

Jung

Kim

et al. 2022

Sci Rep

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Thioacetamide (TAA) was administered orally at 0, 10, and 30 mg/kg body weight (BW) daily to Sprague–Dawley rats aged 6–7 weeks for 28 consecutive days. Nephrotoxicity and proteomics were evaluated in the kidneys of rats exposed to TAA. The BW decreased, however, the relative kidneys weight increased. No significant histopathologic abnormalities were found in the kidneys. The numbers of monocytes and platelets were significantly increased. However, the mean corpuscular volume and hematocrit values were decreased significantly in rats exposed to 30 mg/kg BW TAA. The expression levels of Kim-1 and NGAL were increased 4 to 5-fold in the kidneys, resulting in significant nephrotoxicity. Proteomic analysis was conducted and a total of 5221 proteins spots were resolved. Of these, 3 and 21 protein spots were up- and downregulated, respectively. The validation of seven proteins was performed by Western blot analysis. The expression level of ASAP2 was significantly upregulated, whereas RGS14, MAP7Dl, IL-3Rα, Tmod1, NQO2, and MUP were reduced. Sixteen isoforms of MUP were found by the 2DE immunoblot assay and were significantly downregulated with increasing exposure to TAA. MUP isoforms were compared in the liver, kidneys, and urine of untreated rats and a total of 43 isoforms were found.

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“…Adenovirus of miR-30e, miR-30e antago and adenovirus of miR-30e scramble (Hanbio) were transduction in injured carotid artery; the protocol of this experiment is described in a previous study. 30 Rats were provided with water and food provided ad libitum for 14 days.…”

Section: Vsmc Culture and Carotid Artery Balloon Injury In Ratsmentioning

confidence: 99%

Effect of MicroRNA-30e on the Behavior of Vascular Smooth Muscle Cells via Targeting Ubiquitin-Conjugating Enzyme E2I

Zong

Nai

et al. 2017

Circ J

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Background: Many microRNAs (miRNAs) have recently been shown to demonstrate critical roles in differentiation, proliferation and migration of vascular smooth muscle cells (VSMCs). Methods and Results:In this study, a certain amount of miRNA expression in VSMCs was evaluated by real-time polymerase chain reaction, and it was found that microRNA-30e (miR-30e) was expressed more strongly than other common vascular well-expressed miRNAs in vitro. Subsequently, both a gain and loss of function study was performed in vitro and in vivo. It was found that miR-30e in VSMCs was strongly downregulated concomitantly with stimulation, and miR-30e inhibited VSMCs proliferation and migration both in vitro and in vivo. Furthermore, ubiquitin-conjugating enzyme E2I (Ube2i) was identified as the target gene of endogenous miR-30e by luciferase reporter assay, and it was confirmed that overexpression of miR-30e significantly reduced Ube2i and inhibited the phenotypic switch of VSMCs. Knockdown of Ube2i had an influence over the proliferation and migration of cultured VSMCs, as same as the miR-30e mimic did. Overexpression of miR-30e induced the apoptosis of VSMCs and deregulated the protein expression of IkBα, which is crucial for the NFκB signal pathway. Conclusions:The results of this study indicated that miR-30e in VSMCs exerted an anti-atherosclerosis effect via inhibiting proliferation and migration, and promoting apoptosis of VSMCs. More specifically, it was demonstrated that miR-30e exhibited these effects on VSMCs partially through targeting Ube2i and downregulating the IκBα/NFκB signaling pathway.

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Downregulation of Quinone Reductase 2 Attenuates Vascular Smooth Muscle Cells Proliferation and Neointimal Formation in Balloon Injured Rat Carotid Artery

Cited by 4 publications

References 30 publications

The genomic response of human granulosa cells (KGN) to melatonin and specific agonists/antagonists to the melatonin receptors

The genomic response of human granulosa cells (KGN) to melatonin and specific agonists/antagonists to the melatonin receptors

Nephrotoxicity evaluation and proteomic analysis in kidneys of rats exposed to thioacetamide

Effect of MicroRNA-30e on the Behavior of Vascular Smooth Muscle Cells via Targeting Ubiquitin-Conjugating Enzyme E2I

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