Nintedanib Inhibits VEGF-Induced Neovascularization in Human Conjunctival Vascular Endothelial Cells.

IF 1.5 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Yi Cheng, Tang-Rui Huang, Yi-Ke Yan, Yu-Ting Liao, Hai-Xia Liu
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引用次数: 0

Abstract

Objective: Conjunctival vascularization and fibroblasts are important factors leading to filtering bleb scarring after glaucoma filtering surgery. Previous studies have shown that nintedanib can inhibit the transformation of conjunctival fibroblasts into myofibroblasts, alleviating scar formation. This study aimed to investigate the effect of nintedanib on vascular endothelial growth factor (VEGF)-induced neovascularization of human conjunctival vascular endothelial cells and to reveal the molecular mechanisms involved.

Methods: Primary human conjunctival vascular endothelial cells were cultured with VEGF alone or in combination with nintedanib, and cell proliferation and migration were measured via cell counting kit-8 and scratch assays, respectively. The effect of nintedanib on human conjunctival vascular endothelial cell tube formation was also assayed. The phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) were measured via Western blotting.

Results: VEGF (120 ng/mL) significantly promoted the proliferation of human conjunctival vascular endothelial cells. Nintedanib inhibited the VEGF-induced proliferation of these cells while also suppressing cell migration (P < 0.0001) and vascularization (P < 0.01). Furthermore, nintedanib reduced ERK1/2 (P < 0.01) and JNK phosphorylation (P < 0.001).

Conclusion: Our study provides new evidence that nintedanib inhibits the proliferation, migration, and neovascularization of human conjunctival vascular endothelial cells and downregulates the expression of p-ERK and p-JNK in the MAPK pathway.

尼达尼布抑制vegf诱导的人结膜血管内皮细胞新生血管。
目的:结膜血管形成和成纤维细胞是导致青光眼滤过术后滤过泡瘢痕形成的重要因素。既往研究表明,尼达尼布能抑制结膜成纤维细胞向肌成纤维细胞的转化,减轻瘢痕形成。本研究旨在探讨尼达尼布对血管内皮生长因子(VEGF)诱导的人结膜血管内皮细胞新生血管的影响,并揭示其分子机制。方法:用VEGF单独或联合尼达尼布培养原代人结膜血管内皮细胞,分别用细胞计数试剂盒-8和划痕法检测细胞增殖和迁移。研究了尼达尼布对人结膜血管内皮细胞管形成的影响。Western blotting检测细胞外信号调节激酶1/2 (ERK1/2)和c-Jun n -末端激酶(JNK)的磷酸化水平。结果:VEGF (120 ng/mL)显著促进人结膜血管内皮细胞增殖。结论:我们的研究为尼达尼布抑制人结膜血管内皮细胞的增殖、迁移和新生血管提供了新的证据,并下调了MAPK通路中P - erk和P - jnk的表达。
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来源期刊
Current Medical Science
Current Medical Science Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
4.70
自引率
0.00%
发文量
126
期刊介绍: Current Medical Science provides a forum for peer-reviewed papers in the medical sciences, to promote academic exchange between Chinese researchers and doctors and their foreign counterparts. The journal covers the subjects of biomedicine such as physiology, biochemistry, molecular biology, pharmacology, pathology and pathophysiology, etc., and clinical research, such as surgery, internal medicine, obstetrics and gynecology, pediatrics and otorhinolaryngology etc. The articles appearing in Current Medical Science are mainly in English, with a very small number of its papers in German, to pay tribute to its German founder. This journal is the only medical periodical in Western languages sponsored by an educational institution located in the central part of China.
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