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Inhibitor of RAGE and glucose‑induced inflammation in bone marrow mesenchymal stem cells: Effect and mechanism of action.

Abstract：

:The occurrence and development of hyperglycemia‑induced inflammation is associated with increased expression of receptor for advanced glycation end products (RAGE) and inflammatory factors, including IL‑1β, TNF‑α and IL‑6. Previous studies have reported that the nucleotide‑binding oligomerization domain‑like receptor protein 3 (NLRP3) inflammasome interacts with thioredoxin‑interacting protein (TXNIP) and serves a crucial role in inflammation. FPS‑ZM1 has been identified as target inhibitor of RAGE and has been shown to exert an anti‑inflammatory effect in vitro. However, the underlying mechanism by which FPS‑ZM1 impacts high glucose (HG)‑induced inflammation in bone marrow mesenchymal stem cells (BMSCs) remains unclear. The present study explored the regulatory effect of FPS‑ZM1 on HG‑induced inflammation in BMSCs. Furthermore, the role of the TXNIP/NLRP3 inflammasome signaling pathway in the regulatory effects of FPS‑ZM1 on HG‑induced inflammation was studied. Cell viability was determined using Cell Counting Kit‑8 and western blotting was used to assess the protein expression levels of RAGE. ELISA was used to determine the levels of inflammatory markers. Reverse transcription‑quantitative PCR and western blotting were used to measure the mRNA and protein expression levels of TXNIP, caspase‑1, thioredoxin (TRX), NLRP3 and apoptosis‑related speck‑like protein containing CARD (ASC). The results revealed that in BMSCs, RAGE expression was stimulated by HG, an effect which was reversed by treatment with FPS‑ZM1. In addition, HG activated inflammatory factors, such as TNF‑α, IL‑1β and IL‑6; however, their levels were suppressed when cells were treated with FPS‑ZM1 or the TXNIP/NLRP3 pathway inhibitor, resveratrol (Res). Furthermore, FPS‑ZM1 inhibited the mRNA and protein expression levels of TXNIP, caspase‑1, NLRP3 and ASC, and promoted TRX expression, which was consistent with the effects of Res. These findings indicated that FPS‑ZM1 may attenuate HG‑induced inflammation in BMSCs. Furthermore, the TXNIP/NLRP3 inflammasome signaling pathway mediated the molecular mechanism underlying this effect.

journal_name

Mol Med Rep

journal_title

Molecular medicine reports

authors

Jiang M,Wang X,Wang P,Peng W,Zhang B,Guo L

doi

10.3892/mmr.2020.11422

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

3255-3262

issue

eissn

1791-2997

issn

1791-3004

journal_volume

pub_type

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Inhibitor of RAGE and glucose‑induced inflammation in bone marrow mesenchymal stem cells: Effect and mechanism of action.