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血管内皮生长因子受体 1 在鼻息肉组织中的表达。

Vascular endothelial growth factor receptor 1 expression in nasal polyp tissue.

机构信息

Laboratory of Clinical Immunology, Department of Microbiology and Immunology, Catholic University of Leuven, Leuven, Belgium.

出版信息

Allergy. 2014 Feb;69(2):237-45. doi: 10.1111/all.12277. Epub 2013 Oct 15.

Abstract

BACKGROUND

Edema represents a key feature of nasal polyp (NP) disease. Members of the vascular endothelial growth factor (VEGF) family may be involved, but the precise role of VEGF-A, VEGF-B, placental growth factor (PlGF), and their receptors VEGFR1 and VEGFR2 in NP edema formation remains elusive.

OBJECTIVE

Exploring the expression of VEGF family members and their receptors and their correlation with clinical, radiological, and edema markers in NP.

METHODS

The expression of VEGF-A, VEGF-B, PlGF, VEGFR1, and VEGFR2 was measured in NP (n = 23) and control tissue (n = 22) at mRNA and protein level. Edema was evaluated by measuring albumin levels and wet/dry ratios. Computed tomography (CT) scans were scored using the Lund-Mackay scoring system. IL-5 mRNA expression was determined by real-time RT-PCR. Cell suspensions from NP (n = 10) and control tissue (n = 12) were stimulated in vitro with IL-1β or TNFα.

RESULTS

mRNA expression of VEGFR1 and VEGF-B was significantly higher in NP compared with control tissue. Expression levels of VEGF-B and VEGFR1 significantly correlated with NP albumin content (VEGF-B: P = 0.0208; VEGFR1: P = 0.0293), CT scan scores (VEGF-B: P = 0.0075; VEGFR1: P = 0.0068), and IL-5 mRNA (VEGF-B: P = 0.0027; VEGFR1: P = 0.0001). In vitro stimulation of control and NP tissue cell suspensions with IL-1β or TNFα significantly reduced the expression of VEGFR2 in control tissue, without altering VEGFR1 and VEGF-B expression. hVEGF-B induced nitric oxide production in NP macrophages (P < 0.05).

CONCLUSION

Expression levels of VEGFR1 and VEGF-B correlate with edema and clinical markers of NP disease and therefore represent potential therapeutic targets.

摘要

背景

水肿是鼻息肉(NP)疾病的一个关键特征。血管内皮生长因子(VEGF)家族的成员可能参与其中,但 VEGF-A、VEGF-B、胎盘生长因子(PlGF)及其受体 VEGFR1 和 VEGFR2 在 NP 水肿形成中的确切作用仍不清楚。

目的

探讨 VEGF 家族成员及其受体在 NP 中的表达及其与临床、影像学和水肿标志物的相关性。

方法

在 NP(n=23)和对照组织(n=22)中测量 VEGF-A、VEGF-B、PlGF、VEGFR1 和 VEGFR2 的 mRNA 和蛋白表达水平。通过测量白蛋白水平和湿/干比来评估水肿。使用 Lund-Mackay 评分系统对 CT 扫描进行评分。通过实时 RT-PCR 测定 NP 中 IL-5 mRNA 的表达。用 IL-1β 或 TNFα 体外刺激 NP(n=10)和对照组织(n=12)的细胞悬液。

结果

与对照组织相比,NP 中 VEGFR1 和 VEGF-B 的 mRNA 表达显著升高。VEGF-B 和 VEGFR1 的表达水平与 NP 白蛋白含量显著相关(VEGF-B:P=0.0208;VEGFR1:P=0.0293)、CT 扫描评分(VEGF-B:P=0.0075;VEGFR1:P=0.0068)和 IL-5 mRNA(VEGF-B:P=0.0027;VEGFR1:P=0.0001)。用 IL-1β 或 TNFα 体外刺激对照和 NP 组织细胞悬液可显著降低对照组织中 VEGFR2 的表达,而不改变 VEGFR1 和 VEGF-B 的表达。hVEGF-B 诱导 NP 巨噬细胞产生一氧化氮(P<0.05)。

结论

VEGFR1 和 VEGF-B 的表达水平与 NP 疾病的水肿和临床标志物相关,因此代表潜在的治疗靶点。

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