Oncotarget

Research Papers:

IL-1β-stimulated β-catenin up-regulation promotes angiogenesis in human lung-derived mesenchymal stromal cells through a NF-κB-dependent microRNA-433 induction

Jia Sun, Jintao Chen, Juan Cao, Tianxiang Li, Shaoxia Zhuang and Xiufeng Jiang _

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Oncotarget. 2016; 7:59429-59440. https://doi.org/10.18632/oncotarget.10683

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Abstract

Jia Sun1,*, Jintao Chen1,*, Juan Cao1, Tianxiang Li1, Shaoxia Zhuang1, Xiufeng Jiang1

1Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi 214023, Jiangsu, China

*These authors have contributed equally to this paper

Correspondence to:

Xiufeng Jiang, email: xiufengjiangg@sina.com

Keywords: lung injury, mesenchymal stem cell, angiogenesis, microRNA, Wnt/β-catenin

Received: June 03, 2016    Accepted: July 04, 2016    Published: July 18, 2016

ABSTRACT

Considerable attentions have been focused on the treatment of lung injury using mesenchymal stem cells that can replenish damaged tissues including the blood vessels. In human lung-derived mesenchymal stem cells (hL-MSC), we investigated the potential role of an IL-1β-stimulated miR-433 pathway in angiogenesis in vitro. The expressions of miR-433 and its target genes were examined in cells treated with IL-1β. The angiogenic activity of hL-MSC was studied by cell migration and tube formation assays in which miR-433 levels were manipulated. The reporter assay and chromatin immunoprecipitation (ChIP) were also performed to analyze the underlying regulations. We found that the expression of miR-433 was enhanced in hL-MSC by IL-1β in a NF-κB dependent manner via a NF-κB binding site at its promoter region. The effects of IL-1β on promoting angiogenic activities in hL-MSC can be mimicked by the overexpression of miR-433 and were blocked by anti-miR-433. Mechanistically, our data suggested that miR-433 directly targets the 3’-UTR of Dickkopf Wnt signaling pathway inhibitor 1 (DKK1) mRNA and decreases its expression. Consistently, the expression of β-catenin, the major mediator of canonical Wnt pathway that is capable of inducing endothelial differentiation and angiogenesis, was upregulated by IL-1β through miR-433. Thus, increasing miR-433 expression by IL-1β in mesenchymal stem cells could stimulate their capacity of vascular remodeling for efficient repair processes, which may be utilized as a therapeutic target in patients suffering from severe lung injury.


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