The role of focal adhesion kinase in transforming growth factor-β2 induced migration of human lens epithelial cells

被引：11
作者：
Liu, Jie [1 ,2 ]
Xu, Dan [3 ]
Li, Jingming [1 ]
Gao, Ning [1 ]
Liao, Chongbing [4 ]
Jing, Ruihua [1 ]
Wu, Bogang [5 ]
Ma, Bo [1 ]
Shao, Yongping [3 ,4 ]
Pei, Cheng [1 ]
机构：
[1] Xi An Jiao Tong Univ, Dept Ophthalmol, Med Sch, Affiliated Hosp 1, 277 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China
[2] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA
[3] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Dept Biol Sci & Engn, Key Lab Biomed Informat Engn,Minist Educ, Xian 710049, Shaanxi, Peoples R China
[4] Xi An Jiao Tong Univ, Frontier Inst Sci & Technol, Ctr Translat Med, 28 Xianning West Rd, Xian 710049, Shaanxi, Peoples R China
[5] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA
来源：
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE | 2018年 / 42卷 / 06期
基金：
美国国家科学基金会;
关键词：
transforming growth factor-beta 2; migration; integrin-focal adhesion kinase signaling; POSTERIOR CAPSULE OPACIFICATION; TGF-BETA; CANCER METASTASIS; MESENCHYMAL TRANSITION; DOWN-REGULATION; GROWTH; INTEGRIN; FAK; FIBROSIS; MATRIX;
D O I：
10.3892/ijmm.2018.3912
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
The migration of lens epithelial cells towards the posterior capsule is a key event in the development of posterior capsule opacification (PCO). Accumulating evidence has described crosstalk between growth factors and adhesive signaling pathways in wound healing and cell migration. The aim of the present study was to elucidate an aberrant transforming growth factor (TGF)-beta 2 signaling pathway that regulated the migration of lens epithelial cells in the pathological context of PCO. The expression of fibronectin, focal adhesion kinase (FAK) and phosphorylated (p)-FAK in HLE-B3 cells following TGF-beta 2 treatment was determined by western blot analysis and the expression of integrin alpha 5 beta 1 was detected by flow cytometry. Cell migration capacity was measured by wound healing and Transwell assays in the presence of 1,2,4,5-tetraaminobenzene tetrahydrochloride, a selective FAK inhibitor, fibronectin small interfering RNA interference, arginylglycylaspartic acid peptides or alpha 5 beta 1-integrin neutralizing antibodies. The 1,2,4,5-tetraami-nobenzene tetrahydrochloride was administered daily to 16 rabbits following cataract surgery. Fibronectin and TGF-beta expression were increased in the PCO group, demonstrated by immunofluorescence assays. PCO grading was conducted by slit-lamp biomicroscopy and evaluation of posterior capsule opacification software. It was observed that TGF-2 promoted HLE-B3 cell migration and upregulated fibronectin expression, which was followed by an increased phosphorylation of FAK. In addition, TGF-beta 2 treatment and fibronectin surface coating significantly increased cell migration and FAK activation, which was inhibited by disrupting fibronectin-integrin 51 interaction with the arginylglycylaspartic acid peptide, 51-integrin neutralizing antibody or fibronectin depletion. Finally, suppression of FAK signaling by its inhibitor signifi-cantly decreased cell migration in vitro and attenuated PCO development in vivo. In summary, TGF-beta 2 was indicated to promote the migration of lens epithelial cells through the TGF-beta 2/fibronectin/integrin/FAK axis. Inhibition of FAK activity decreased TGF-beta 2-mediated cell migration in vitro and improved the symptoms of PCO in a rabbit model.
引用
收藏
页码：3591 / 3601
页数：11
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