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

Liu,Jie; Xu,Dan; Li,Jingming; Gao,Ning; Liao,Chongbing; Jing,Ruihua; Wu,Bogang; Ma,Bo; Shao,Yongping; Pei,Cheng

doi:10.3892/ijmm.2018.3912

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

Authors:
- Jie Liu
- Dan Xu
- Jingming Li
- Ning Gao
- Chongbing Liao
- Ruihua Jing
- Bogang Wu
- Bo Ma
- Yongping Shao
- Cheng Pei
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Affiliations: Department of Ophthalmology, First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Key Laboratory of Biomedical Information Engineering of the Ministry of Education, Department of Biological Science and Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, P.R. China, Center for Translational Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, P.R. China, Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
Published online on: October 2, 2018 https://doi.org/10.3892/ijmm.2018.3912
Pages: 3591-3601

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Abstract

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)‑β2 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‑β2 treatment was determined by western blot analysis and the expression of integrin α5β1 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 α5β1‑integrin neutralizing antibodies. The 1,2,4,5‑tetraaminobenzene tetrahydrochloride was administered daily to 16 rabbits following cataract surgery. Fibronectin and TGF‑β 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‑β2 promoted HLE‑B3 cell migration and upregulated fibronectin expression, which was followed by an increased phosphorylation of FAK. In addition, TGF‑β2 treatment and fibronectin surface coating significantly increased cell migration and FAK activation, which was inhibited by disrupting fibronectin‑integrin α5β1 interaction with the arginylglycylaspartic acid peptide, α5β1‑integrin neutralizing antibody or fibronectin depletion. Finally, suppression of FAK signaling by its inhibitor significantly decreased cell migration in vitro and attenuated PCO development in vivo. In summary, TGF‑β2 was indicated to promote the migration of lens epithelial cells through the TGF‑β2/fibronectin/integrin/FAK axis. Inhibition of FAK activity decreased TGF‑β2‑mediated cell migration in vitro and improved the symptoms of PCO in a rabbit model.

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