Phosphorylation of STAT3 and ERBB2 mediates hypoxia‑induced VEGF release in ARPE‑19 cells

Hwang,Soohyun; Seong,Hyemin; Ryu,Jinhyun; Jeong,Joo   Yeon; Kang,Tae   Seen; Nam,Ki  Yup; Seo,Seong   Wook; Kim,Seong   Jae; Kang,Sang  Soo; Han,Yong   Seop

doi:10.3892/mmr.2020.11344

Phosphorylation of STAT3 and ERBB2 mediates hypoxia‑induced VEGF release in ARPE‑19 cells

Authors:
- Soohyun Hwang
- Hyemin Seong
- Jinhyun Ryu
- Joo Yeon Jeong
- Tae Seen Kang
- Ki Yup Nam
- Seong Wook Seo
- Seong Jae Kim
- Sang Soo Kang
- Yong Seop Han
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Affiliations: Department of Anatomy and Convergence Medical Science, College of Medicine, Gyeongsang National University, Jinju, South Gyeongsang 52727, Republic of Korea, Department of Ophthalmology, Gyeongsang National University Changwon Hospital, Changwon, Gyeongsangnam‑do 51472, Republic of Korea, Department of Ophthalmology, College of Medicine, Gyeongsang National University, Jinju, South Gyeongsang 52727, Republic of Korea
Published online on: July 16, 2020 https://doi.org/10.3892/mmr.2020.11344
Pages: 2733-2740
Copyright: © Hwang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Neovascularization in the retina can cause loss of vision. Vascular endothelial growth factor (VEGF) serves an important role in the pathogenesis of retinal vascular diseases. Hypoxia is a notable cause of VEGF release and both STAT3 and ERBB2 are known to be associated with VEGF. In addition, STAT3 and ERBB2 interact with each other. In the present study, it was hypothesized that signal transducer and activator of transcription 3 (STAT3) and erbB‑2 receptor tyrosine kinase 2 (ERBB2) may be involved in the regulation of hypoxia‑induced VEGF in the retina. Cells of the retinal pigment epithelium (RPE) are an important source of VEGF. Therefore, the RPE‑derived human cell line ARPE‑19 was exposed to hypoxia. Hypoxia‑induced phosphorylation of STAT3 and ERBB2 in ARPE‑19 cells was decreased by AG490, an inhibitor of Janus kinase 2, as were hypoxia‑induced VEGF release and tube formation in human umbilical vein endothelial cells. Thus, phosphorylation of ERBB2 and STAT3 regulates hypoxia‑induced VEGF release in ARPE‑19 cells. The results of the present study suggested that inhibition of ERBB2 and STAT3‑mediated pathways under hypoxia may represent a new strategy for treating retinal vascular disease.

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