PMID- 34149879 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210622 IS - 1792-0981 (Print) IS - 1792-1015 (Electronic) IS - 1792-0981 (Linking) VI - 22 IP - 2 DP - 2021 Aug TI - Protective role and molecular mechanism of action of Nesfatin-1 against high glucose-induced inflammation, oxidative stress and apoptosis in retinal epithelial cells. PG - 833 LID - 10.3892/etm.2021.10265 [doi] LID - 833 AB - 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-kappaB, 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-kappaB/NLRP3 inflammasome signaling and the expression of HMGB1 were inhibited by nesfatin-1. Furthermore, HMGB1 overexpression partially abrogated the inactivation of the NF-kappaB/NLRP3 inflammasome pathway caused by nesfatin-1. Taken together, these findings demonstrated that nesfatin-1 inhibited the activation of the NF-kappaB/NLRP3 inflammasome signaling via modulating HMGB1 and exerted a protective effect on ARPE-19 cells against high glucose-induced inflammation, oxidative stress and apoptosis. CI - Copyright: (c) Sun et al. FAU - Sun, Haiyan AU - Sun H AD - Ophthalmology Department, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China. FAU - Zhao, Huahui AU - Zhao H AD - Ophthalmology Department, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China. FAU - Yan, Zhipeng AU - Yan Z AD - Ophthalmology Department, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China. FAU - Liu, Xiaokun AU - Liu X AD - Ophthalmology Department, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China. FAU - Yin, Pengfei AU - Yin P AD - Ophthalmology Department, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China. FAU - Zhang, Jun AU - Zhang J AD - Ophthalmology Department, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China. LA - eng PT - Journal Article DEP - 20210603 PL - Greece TA - Exp Ther Med JT - Experimental and therapeutic medicine JID - 101531947 PMC - PMC8200809 OTO - NOTNLM OT - LRR and PYD domains-containing protein 3 OT - NACHT OT - diabetic retinopathy OT - high glucose OT - high-mobility group protein B1 OT - nesfatin-1 COIS- The authors declare that they have no competing interests. EDAT- 2021/06/22 06:00 MHDA- 2021/06/22 06:01 PMCR- 2021/06/03 CRDT- 2021/06/21 05:53 PHST- 2020/09/11 00:00 [received] PHST- 2021/01/21 00:00 [accepted] PHST- 2021/06/21 05:53 [entrez] PHST- 2021/06/22 06:00 [pubmed] PHST- 2021/06/22 06:01 [medline] PHST- 2021/06/03 00:00 [pmc-release] AID - ETM-0-0-10265 [pii] AID - 10.3892/etm.2021.10265 [doi] PST - ppublish SO - Exp Ther Med. 2021 Aug;22(2):833. doi: 10.3892/etm.2021.10265. Epub 2021 Jun 3.