Oncotarget

Research Papers:

Caveolin-1 scaffolding domain peptides enhance anti-inflammatory effect of heme oxygenase-1 through interrupting its interact with caveolin-1

Ping Weng, Xiao-Tong Zhang, Qiong Sheng, Wen-Fang Tian, Jun-Liang Chen, Jia-Jia Yuan, Ji-Ru Zhang and Qing-Feng Pang _

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Oncotarget. 2017; 8:40104-40114. https://doi.org/10.18632/oncotarget.16676

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Abstract

Ping Weng1,*, Xiao-Tong Zhang1,*, Qiong Sheng1, Wen-Fang Tian1, Jun-Liang Chen1, Jia-Jia Yuan1, Ji-Ru Zhang2 and Qing-Feng Pang1

1 Wuxi Medical School, Jiangnan University, Wuxi, China

2 Department of Anesthesiology, the Affiliated Hospital of Jiangnan University, Wuxi, China

* Co-first author

Correspondence to:

Qing-feng Pang, email:

Keywords: acute lung injury, lipopolysaccharide, heme oxygenase-1, caveolin-1, caveolin-1 scaffolding domain peptide

Received: January 18, 2017 Accepted: March 19, 2017 Published: March 29, 2017

Abstract

Caveolin-1(Cav-1) scaffolding domain (CSD) peptides compete with the plasma membrane Cav-1, inhibit the interaction of the proteins and Cav-1, and re-store the functions of Cav-1 binding proteins. Heme oxygenase-1 (HO-1) binds to Cav-1 and its enzymatic activity was inhibited. In this study, we investigated the effect of CSD peptides on interaction between HO-1 and Cav-1, and on the HO-1 activity in vitro and in vivo. Our data showed that CSD peptides decreased the compartmentalization of HO-1 and Cav-1, and increased the HO-1 activity both in LPS-treated alveolar macrophages and in mice. Meanwhile, CSD peptides obviously ameliorated the pathology changes in mice and lowered the following injury indexes: the wet/dry ratio of lung tissues, total cell numbers in bronchoalveolar lavage fluid and lactate dehydrogenase activity in the serum. Mechanistically, it was firstly found that CSD peptides promoted alveolar macrophages polarization to M2 phenotype and inhibited the IκB degeneration. Furthermore, CSD peptides down-regulated the expression of IL-1β, IL-6, TNF-α, MCP-1, and iNOS in alveolar macrophages and in lung tissue. However, the protective role of CSD peptides on LPS-induced acute lung injury in mice could be abolished by zinc protoporphyrin IX (ZnPP, a HO-1 activity inhibitor). In summary, CSD peptides have beneficial anti-inflammatory effects by restoring the HO-1 activity suppressed by Cav-1 on plasma membrane.


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