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新型肽 NT/K-CFY 源自神经蛋白酶抑制剂的 kringle 结构,可抑制血管新生。

Novel Peptide NT/K-CFY Derived from Kringle Structure of Neurotrypsin Inhibits Neovascularization.

机构信息

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

National Clinical Research Center for Eye Diseases, Shanghai, China.

出版信息

Curr Eye Res. 2021 Oct;46(10):1551-1558. doi: 10.1080/02713683.2021.1907417. Epub 2021 Apr 19.

Abstract

: To assess the anti-neovascularization effect of a novel peptide NT/K-CFY derived from the kringle domain of neurotrypsin.: Cell migration, lumen formation and cell proliferation assays were performed to determine the anti-neovascularization effect of NT/K-CFY in primary human umbilical vein endothelial cells (HUVECs). Chick chorioallantoic membrane (CAM) and oxygen-induced retinopathy (OIR) models were established to assess the anti-angiogenic role of NT/K-CFY . The retinal expression of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) was examined by western blot and real-time PCR in OIR model.: The results showed that NT/K-CFY effectively and safely decreased VEGF-induced cell migration, cell proliferation and tube formation in HUVECs. In addition, NT/K-CFY showed certain efficacy in angiogenesis inhibition in chicken embryos and oxygen-treated mouse pups. Moreover, the CFY peptide also improved retinal blood perfusion and reversed the abnormal expression of VEGF and PEDF in OIR mouse model.: NT/K-CFY peptide strongly inhibits neovascularization . This novel peptide may become a promising therapeutic agent for ocular angiogenesis-related diseases.

摘要

评估新型肽 NT/K-CFY 对神经蛋白酶kringle 结构域的抗血管生成作用:通过细胞迁移、管腔形成和细胞增殖实验来确定 NT/K-CFY 在原代人脐静脉内皮细胞(HUVEC)中的抗血管生成作用。建立鸡胚绒毛尿囊膜(CAM)和氧诱导视网膜病变(OIR)模型,评估 NT/K-CFY 的抗血管生成作用。通过 Western blot 和实时 PCR 检测 OIR 模型中血管内皮生长因子(VEGF)和色素上皮衍生因子(PEDF)的视网膜表达。结果表明,NT/K-CFY 可有效且安全地抑制 VEGF 诱导的 HUVEC 细胞迁移、增殖和管腔形成。此外,NT/K-CFY 在鸡胚和氧处理的小鼠幼仔中对血管生成抑制具有一定疗效。此外,CFY 肽还改善了 OIR 小鼠模型中的视网膜血流灌注,并逆转了 VEGF 和 PEDF 的异常表达。NT/K-CFY 肽强烈抑制新生血管形成。这种新型肽可能成为治疗与眼部血管生成相关疾病的有前途的治疗剂。

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