Protective role and molecular mechanism of action of Nesfatin‑1 against high glucose‑induced inflammation, oxidative stress and apoptosis in retinal epithelial cells

Sun,Haiyan; Zhao,Huahui; Yan,Zhipeng; Liu,Xiaokun; Yin,Pengfei; Zhang,Jun

doi:10.3892/etm.2021.10265

Protective role and molecular mechanism of action of Nesfatin‑1 against high glucose‑induced inflammation, oxidative stress and apoptosis in retinal epithelial cells

Authors:
- Haiyan Sun
- Huahui Zhao
- Zhipeng Yan
- Xiaokun Liu
- Pengfei Yin
- Jun Zhang
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Affiliations: Ophthalmology Department, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
Published online on: June 3, 2021 https://doi.org/10.3892/etm.2021.10265
Article Number: 833
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Diabetic retinopathy (DR) is a major complication of diabetes mellitus that may cause severe visual impairment. It has been reported that the levels of nesfatin‑1 in the serum and vitreous humor were negatively correlated with DR; however, its role in DR has not been fully elucidated. Therefore, the present study was performed to investigate the effect of nesfatin‑1 on high glucose‑treated human retinal epithelial cells (ARPE‑19) and explore the underlying mechanism. The effects of nesfatin‑1 on cell viability, inflammation, oxidative stress and apoptosis were examined under high glucose conditions. The Cell Counting Kit‑8 assay was used to determine cell viability. The levels of inflammatory cytokines were evaluated using ELISA kits. The reactive oxygen species and malondialdehyde content was estimated using commercial assay kits. Flow cytometry was performed to detect apoptotic cells and western blot analysis was employed to evaluate the expression of apoptosis‑associated proteins. Moreover, the levels of NF‑κB, NACHT, LRR and PYD domains‑containing protein 3 (NLRP3) and high‑mobility group protein B1 (HMGB1) were determined via western blot analysis. The results revealed that nesfatin‑1 enhanced cell viability and suppressed inflammation, oxidative stress and apoptosis in the presence of high glucose concentration. Moreover, the activation of the NF‑κB/NLRP3 inflammasome signaling and the expression of HMGB1 were inhibited by nesfatin‑1. Furthermore, HMGB1 overexpression partially abrogated the inactivation of the NF‑κB/NLRP3 inflammasome pathway caused by nesfatin‑1. Taken together, these findings demonstrated that nesfatin‑1 inhibited the activation of the NF‑κB/NLRP3 inflammasome signaling via modulating HMGB1 and exerted a protective effect on ARPE‑19 cells against high glucose‑induced inflammation, oxidative stress and apoptosis.

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