Bradykinin potentially stimulates cell proliferation in rabbit corneal endothelial cells through the ZO‑1/ZONAB pathway

He,Lixian; Zhou,Zhou; Shao,Yi; Yang,Zhen; Zhou,Shuangshuang; Zou,Xuexiang; Zhou,Ying; Tan,Gang

doi:10.3892/ijmm.2018.3580

Bradykinin potentially stimulates cell proliferation in rabbit corneal endothelial cells through the ZO‑1/ZONAB pathway

Authors:
- Lixian He
- Zhou Zhou
- Yi Shao
- Zhen Yang
- Shuangshuang Zhou
- Xuexiang Zou
- Ying Zhou
- Gang Tan
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Affiliations: Department of Ophthalmology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China, Medical College, University of South China, Hengyang, Hunan 421001, P.R. China, Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, Nanchang, Jiangxi 330006, P.R. China, Department of Cardiology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China
Published online on: March 22, 2018 https://doi.org/10.3892/ijmm.2018.3580
Pages: 71-80
Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Bradykinin (BK) has been demonstrated to induce proliferation in several types of cell in ex vivo corneas. However, the mechanisms underlying the action of BK on corneal endothelial cells (CECs) remain largely unknown. The present study aimed to investigate the effect of BK on rabbit corneal endothelial cell (RCEC) proliferation, and assess the involvement of the zonula occludens‑1(ZO‑1)/ZO‑1associated nucleic acid binding protein (ZONAB) pathway. Cell proliferation and cell cycle distribution was analyzed following treatment with BK (0.01, 0.1,1.0 or 10.0 µM) for the indicated time intervals (24, 48, 72 and 96 h), or following BK treatment combined with transfection of ZONAB‑small interfering (si)RNA for 72 h. In addition, the expression of tight junction ZO‑1, nuclear ZONAB, proliferating cell nuclear antigen(PCNA) and cyclin D1 were evaluated using western blotting or immunofluorescence. BK treatment was demonstrated to induce time‑ and concentration‑dependent cell proliferation and cell cycle progression, along with the upregulation of tight junction ZO‑1 and nuclear ZONAB, as well as PCNA and cyclin D1 protein expression. Furthermore, knockdown with ZONAB‑siRNA inhibited cell proliferation, induced cell cycle arrest and downregulated PCNA and cyclin D1 protein expression. ZONAB knockdown therefore successfully reversed the increase in proliferation induced by BK treatment. Taken together, these results suggested that BK stimulated RCEC proliferation, potentially via the ZO‑1/ZONAB pathway. The signaling paradigm disclosed in the present study potentially serves as an important therapeutic target for cornea regeneration and transplantation.

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