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Propranolol ameliorates retinopathy of prematurity in mice by downregulating HIF-1α via the PI3K/Akt/ERK pathway

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机构： [1]Department of Neonatology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China [2]Department of Neonatology, ShenzhenChildren’s Hospital, Shenzhen, China [3]Department of Neonatology, Capital Institute of Pediatrics, Beijing, China [4]Department of Endocrinology, Beijing Tongren Hospital, CapitalMedical University, Beijing, China [5]Department of Neonatology, Children’s Hospital, Capital Institute of Pediatrics, Beijing, China

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Retinopathy of prematurity (ROP) is the leading cause of blindness in infants, and elevation of HIF-1α through the PI3K/Akt and ERK pathways is implicated in ROP pathogenesis. The mechanism of action of propranolol in ROP remains controversial. We investigated the effect of propranolol on ROP and explored its potential mechanisms of action in an oxygen-induced retinopathy (OIR) mouse model.OIR mice were first treated with propranolol intraperitoneally, and the retina integrity was measured by FITC-dextran and hematoxylin-eosin staining. The expression of HIF-1α, VEGF, and key signaling pathway proteins was determined using real-time PCR and western blotting.FITC-dextran staining showed that propranolol treatment reduced damage to retinal morphology in OIR mice. Mice treated with propranolol showed a reduced number of nuclei of vascular endothelial cells penetrating the inner limiting membrane of the retina, confirming the therapeutic effect of propranolol on ROP. Further analysis showed that HIF-1α and PI3K/Akt/ERK pathway protein levels were significantly elevated in OIR mice. In contrast, propranolol treatment downregulated the expression of these proteins, indicating that the PI3K/Akt/ERK/HIF-1α axis is associated with propranolol-induced ROP alleviation.Propranolol has a therapeutic function against ROP, likely through the downregulation of HIF-1α via the PI3K/Akt/ERK pathway.Propranolol can reduce the formation of abnormal retinal neovascularization in oxygen-induced retinopathy (OIR) models, and reduce leaking, tortuous, and abnormally expanding retinal blood vessels. Propranolol possibly improves OIR by inhibiting the activated ERK and HIF-1α pathways. Furthermore, propranolol may downregulate HIF-1α via the PI3K/Akt/ERK pathway to ameliorate retinopathy of prematurity. This study elucidated that the therapeutic effect of propranolol in OIR mice does not involve the VEGFR-2 pathway.© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.

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出版当年[2022]版：

大类 | 3 区医学

小类 | 2 区儿科

最新[2023]版：

大类 | 3 区医学

小类 | 2 区儿科

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Q1 PEDIATRICS

最新[2023]版：

Q1 PEDIATRICS

影响因子： 3.1 最新[2023版] 3.5 最新五年平均 3.953 出版当年[2021版] 4.15 出版当年五年平均 3.756 出版前一年[2020版] 3.6 出版后一年[2022版]

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第一作者机构： [1]Department of Neonatology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China [2]Department of Neonatology, ShenzhenChildren’s Hospital, Shenzhen, China

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