Regulatory mechanism of NOV/CCN3 in the inflammation and apoptosis of lung epithelial alveolar cells upon lipopolysaccharide stimulation

Zhu,Hai‑Ping; Huang,Hui‑Ya; Wu,Deng‑Min; Dong,Nian; Dong,Li; Chen,Cheng‑Shui; Chen,Chao‑Lei; Chen,Yu‑Guo

doi:10.3892/mmr.2019.10655

Regulatory mechanism of NOV/CCN3 in the inflammation and apoptosis of lung epithelial alveolar cells upon lipopolysaccharide stimulation

Authors:
- Hai‑Ping Zhu
- Hui‑Ya Huang
- Deng‑Min Wu
- Nian Dong
- Li Dong
- Cheng‑Shui Chen
- Chao‑Lei Chen
- Yu‑Guo Chen
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Affiliations: Department of Emergency Medicine and Chest Pain Center, Clinical Research Center for Emergency and Critical Care Medicine of Shandong, Key Laboratory of Emergency and Critical Care Medicine, Key Laboratory of Cardiopulmonary‑Cerebral Resuscitation Research, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Intensive Care Unit, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Rehabilitation Medicine, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: September 9, 2019 https://doi.org/10.3892/mmr.2019.10655
Pages: 1872-1880
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lipopolysaccharide (LPS) induces stress inflammation and apoptosis. Pulmonary epithelial cell apoptosis, which accelerates the progression of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), is the leading cause of mortality in patients with ALI/ARDS. The nephroblastoma overexpressed protein (CCN3), an inflammatory modulator, is reported to be a biomarker in ALI. Using the LPS-induced ALI model, this study investigated the expression of CCN3 and its possible molecular mechanism in lung alveolar epithelial cell inflammation and apoptosis. Our data revealed that LPS treatment greatly increased the level of CCN3 in A549 cells. The A549 cells were transfected with specific CCN3 small interfering RNA (siRNA) using transfection reagent. CCN3 siRNA not only largely attenuated the expressions of the inflammatory cytokines interleukin (IL)-1β and transforming growth factor (TGF)-β1, but also reduced the apoptotic rate of the AEC II cells and affected the expressions of the apoptosis-associated proteins (Bcl-2 and caspase-3). Furthermore, CCN3 knockdown greatly inhibited the activation of nuclear factor-κB p65 in A549 cells. In addition, TGF-β/p-Smad inhibitor (TP0427736) and NF-κB inhibitor (PDTC) significantly attenuated the expression level of CCN3 in A549 cells. In conclusion, our data indicated that CCN3 siRNA affected downstream signal through TGF-β/ p-Smad or NF-κB pathway, leading to the inhibition of cell inflammation and apoptosis in human alveolar epithelial cells.

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