Anagliptin alleviates lipopolysaccharide‑induced inflammation, apoptosis and endothelial dysfunction of lung microvascular endothelial cells

Zhang,Jingli; Liu,Lixia

doi:10.3892/etm.2021.10907

Anagliptin alleviates lipopolysaccharide‑induced inflammation, apoptosis and endothelial dysfunction of lung microvascular endothelial cells

Authors:
- Jingli Zhang
- Lixia Liu
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Affiliations: Department of Pharmacy, Taihe County People's Hospital, Fuyang, Anhui 236600, P.R. China, Department of Respiration, No. 984 Hospital, Joint Logistics Support Force of Chinese People's Liberation Army, Beijing 100094, P.R. China
Published online on: October 22, 2021 https://doi.org/10.3892/etm.2021.10907
Article Number: 1472
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

It has been reported that dipeptidyl peptidase‑4 (DPP4) inhibition protects against acute lung injury (ALI). Anagliptin is a novel selective inhibitor of DPP4 but its role in ALI has not been studied. The present study aimed to investigate the effects of anagliptin on lipopolysaccharide (LPS)‑induced human pulmonary microvascular endothelial cell (HPMVEC) injury, as well as its underlying mechanism. HPMVECs were exposed to LPS in the presence or absence of anagliptin co‑treatment. MTT assay was used to evaluate cell viability and nitric oxide (NO) production was detected using a commercial kit. DPP4 and pro‑inflammatory cytokine expression levels, apoptosis and migration were assessed via reverse transcription‑quantitative PCR, western blotting, TUNEL staining and wound healing assay, respectively. Western blot analysis was performed to assess expression levels of proteins involved in NF‑κB signaling, cell apoptosis and migration, as well as high mobility group box 1 (HMGB1)/receptor for advanced glycation end products (RAGE). LPS decreased cell viability and NO production, but elevated expression of DPP4 in HPMVECs. LPS promoted pro‑inflammatory cytokine expression, NF‑κB activation and cell apoptosis, but inhibited cell migration and phosphorylated‑AKT/endothelial NO synthase expression. Anagliptin co‑treatment significantly restored all of these effects. Mechanistically, the upregulation of HMGB1/RAGE expression induced by LPS was markedly blocked by anagliptin. In conclusion, anagliptin alleviated inflammation, apoptosis and endothelial dysfunction in LPS‑induced HPMVECs via modulating HMGB1/RAGE expression. These data provide a basis for use of anagliptin in ALI treatment.

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