Antiangiogenic Effects of Doxazosin on Experimental Choroidal Neovascularization in Mice

GuoJiaxian,; LuoXueting,; LiangJian,; XiaoMeichun,; SunXiaodong,

doi:10.1089/jop.2016.0153

Cited by 9 publications

(7 citation statements)

References 32 publications

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“…Zhang et al, 2018;Zheng et al, 2017), while the PI3K/Akt/mTOR signaling pathway has been proved to play important roles in diabetic retinopathy (Jacot & Sherris, 2011) and choroidal neovascularization (J. Guo, Luo, Liang, Xiao, & Sun, 2017). Our present study revealed that Akt signaling and EGFR were downregulated by KCNQ1OT1 knockdown or by miR-1470 overexpression.…”

Section: Discussionsupporting

confidence: 49%

KCNQ1OT1 affects the progression of diabetic retinopathy by regulating miR‐1470 and epidermal growth factor receptor

Shao

Yin

Fan

et al. 2019

Journal Cellular Physiology

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Long noncoding RNAs have been reported to play important roles in the pathogenesis of diabetic retinopathy (DR), which has been considered as the most common disease leading to vision loss. However, it is still unclear whether KCNQ1 overlapping transcript 1 (KCNQ1OT1) could affect DR. In this study, regarding quantitative reverse transcription polymerase chain reaction assay, KCNQ1OT1 level was upregulated while microRNA‐1470 (miR‐1470) was decreased in DR patients and human retinal endothelial cells. High KCNQ1OT1 expression was correlated with DR stage and low visual function. Using miR‐1470 mimic or knockdown of KCNQ1OT1 could lead to the similar phenomenon; phospho‐AKT, Bax, B‐cell lymphoma 2, and cleaved poly‐ADP ribose polymerase (PARP) were regulated, while vascularization was inhibited and apoptosis was promoted. Regarding bioinformatics analysis and in vitro dual luciferase reporter assay, there should be a negative correlation between KCNQ1OT1 and miR‐1470. Additionally, mRNA of epidermal growth factor receptor (EGFR) was proved as the target of miR‐1470 and EGFR targeting by miR‐1470 initiated KCNQ1OT1 deficiency‐induced apoptosis and promoted proliferation. KCNQ1OT1 and miR‐1470 were proved to be the promoter and repressor of EGFR, respectively. The results suggested that KCNQ1OT1 could sponge miR‐1470 and further regulate EGFR in DR.

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Section: Discussionsupporting

confidence: 49%

KCNQ1OT1 affects the progression of diabetic retinopathy by regulating miR‐1470 and epidermal growth factor receptor

Shao

Yin

Fan

et al. 2019

Journal Cellular Physiology

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“… 44 IGFBPrP1 promotes autophagy and HSC activation by mutually regulating H19 and the PI3K/AKT/mTOR pathway. 45 The PI3K/Akt/mTOR pathway is crucial for autophagy in activated HSCs, 11 and the antiangiogenic effect of doxazosin on experimental choroidal neovascularization has been suggested to be closely associated with the PI3K/Akt/mTOR pathway; 46 thus, we hypothesize that this is the dominant signaling pathway by which doxazosin, autophagy, apoptosis, and HSC activation are associated. Therefore, we first measured the levels of p-PI3K, p-Akt, and p-mTOR in doxazosin-treated HSCs, revealing that they were dose- and time-dependently significantly increased and thereby demonstrating that doxazosin activated the PI3K/Akt/mTOR pathway to a certain extent.…”

Section: Discussionmentioning

confidence: 90%

Doxazosin Attenuates Liver Fibrosis by Inhibiting Autophagy in Hepatic Stellate Cells via Activation of the PI3K/Akt/mTOR Signaling Pathway

Xiu¹,

Ding²,

Li³

et al. 2021

DDDT

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“…Angiogenesis is one of the most major hypoxia responses that can be mediated by the HIF/VEGF axis [13,24]. To date, several studies have been conducted to reveal the effect of HIF inhibition on ocular neovascularization [14,15,25,26]. Previously, we demonstrated that RPE-specific HIF knockout mice showed a significant reduction in laser-induced CNV volume when compared with VEGF knockout mice [14].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effect of Garcinia cambogia Extract and Hydroxycitric Acid Inhibiting Hypoxia-Inducible Factor in a Murine Model of Age-Related Macular Degeneration

Ibuki

Shoda

Miwa

et al. 2019

IJMS

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Background: Age-related macular degeneration (AMD) is the leading cause of blindness and can be classified into two types called atrophic AMD (dry AMD) and neovascular AMD (wet AMD). Dry AMD is characterized by cellular degeneration of the retinal pigment epithelium, choriocapillaris, and photoreceptors. Wet AMD is characterized by the invasion of abnormal vessels from the choroid. Although anti-vascular endothelial growth factor (VEGF) therapy has a potent therapeutic effect against the disease, there is a possibility of chorio-retinal atrophy and adverse systemic events due to long-term robust VEGF antagonism. We focused on hypoxia-inducible factor (HIF) regulation of VEGF transcription, and report the suppressive effects of HIF inhibition against ocular phenotypes in animal models. Many of the known HIF inhibitors are categorized as anti-cancer drugs, and their systemic side effects are cause for concern in clinical use. In this study, we explored food ingredients that have HIF inhibitory effects and verified their effects in an animal model of AMD. Methods: Food ingredients were screened using a luciferase assay. C57BL6/J mice were administered the Garcinia cambogia extract (Garcinia extract) and hydroxycitric acid (HCA). Choroidal neovascularization (CNV) was induced by laser irradiation. Results: Garcinia extract and HCA showed inhibitory effects on HIF in the luciferase assay. The laser CNV model mice showed significant reduction of CNV volume by administering Garcinia extract and HCA. Conclusions: Garcinia extract and HCA showed therapeutic effects in a murine AMD model.

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Antiangiogenic Effects of Doxazosin on Experimental Choroidal Neovascularization in Mice

Abstract: Doxazosin exerts antiangiogenic actions in an experimental mouse model of CNV and may be a potential adjunctive therapy for neovascular age-related macular degeneration in humans.

Cited by 9 publications

References 32 publications

KCNQ1OT1 affects the progression of diabetic retinopathy by regulating miR‐1470 and epidermal growth factor receptor

KCNQ1OT1 affects the progression of diabetic retinopathy by regulating miR‐1470 and epidermal growth factor receptor

Doxazosin Attenuates Liver Fibrosis by Inhibiting Autophagy in Hepatic Stellate Cells via Activation of the PI3K/Akt/mTOR Signaling Pathway

Therapeutic Effect of Garcinia cambogia Extract and Hydroxycitric Acid Inhibiting Hypoxia-Inducible Factor in a Murine Model of Age-Related Macular Degeneration

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