Differential roles of p38 MAPK and ERK1/2 in angiopoietin‑2‑mediated rat pulmonary microvascular endothelial cell apoptosis induced by lipopolysaccharide

Li,Shi; Zhong,Mingmei; Yuan,Yuan; Zhang,Lin

doi:10.3892/etm.2018.6810

Differential roles of p38 MAPK and ERK1/2 in angiopoietin‑2‑mediated rat pulmonary microvascular endothelial cell apoptosis induced by lipopolysaccharide

Authors:
- Shi Li
- Mingmei Zhong
- Yuan Yuan
- Lin Zhang
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Affiliations: ICU, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230061, P.R. China, The Central Laboratory of Binhu Hospital, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230061, P.R. China
Published online on: October 1, 2018 https://doi.org/10.3892/etm.2018.6810
Pages: 4729-4736

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Abstract

Angiopoietin‑2 (Ang‑2) is a Tie‑2 ligand that destabilizes vascular structures, enhances vascular permeability and induces vascular regression and endothelial cell apoptosis. Although there is evidence for the involvement of the Ang/Tie2 axis in acute lung injury (ALI), the underlying mechanisms involved in Ang‑2‑induced cell apoptosis are not well understood. In this study, whether Ang‑2 contributes to microvascular endothelial cell injury and mediates lipopolysaccharide (LPS)‑induced endothelial cell apoptosis and its associated signaling pathways was investigated. Exposure of rat pulmonary microvascular endothelial cells (RPMVECs) to LPS, Ang‑2 and related inhibitors was performed to measure the expression levels of Ang‑2, the activation of mitogen‑activated protein kinases (MAPKs), the phosphorylation of extracellular signal‑regulated kinase (ERK)1/2, and expression of the apoptosis‑related proteins Bax and Bcl‑2 using western blotting, reverse transcription‑quantitative polymerase chain reaction, flow cytometry and fluorescence microscopy. The expression of Ang‑2 in the RPMVECs was increased by LPS independent of time. The phosphorylation of p38 MAPK and ERK1/2 was significantly upregulated and the activation of apoptosis‑related proteins Bax and Bcl was mediated by Ang‑2. In addition, inhibition of the p38 pathway by SB203580 attenuated the Ang‑2‑mediated cell apoptosis, but inhibition of the ERK1/2 pathway by PD98059 exerted an anti‑apoptotic effect against Ang‑2. In conclusion, LPS‑induced apoptosis is partly mediated via stimulation of p38 and ERK1/2 signaling pathways, where Ang‑2 acts an inflammation‑related factor to participate in the course of cell apoptosis in RPMVECs.

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