title: IL-1β-stimulated β-catenin up-regulation promotes angiogenesis in human lung-derived mesenchymal stromal cells through a NF-κB-dependent microRNA-433 induction.
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.
authors.affiliation: Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214023, Jiangsu, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Sun
authors.affiliation: Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214023, Jiangsu, China.
authors.forename: Jintao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214023, Jiangsu, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Cao
authors.affiliation: Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214023, Jiangsu, China.
authors.forename: Tianxiang
authors.initials: T
authors.lastname: Li
authors.affiliation: Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214023, Jiangsu, China.
authors.forename: Shaoxia
authors.initials: S
authors.lastname: Zhuang
authors.affiliation: Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214023, Jiangsu, China.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Jiang
mesh_terms: D002465:Cell Movement; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000166:cytology*; D055370:Lung Injury / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D018919:Neovascularization, Physiologic; D038081:Organogenesis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015854:Up-Regulation; D066253:Vascular Remodeling / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta; C548883:MIRN433 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D051176:beta Catenin
keywords: Wnt/β-catenin; angiogenesis; lung injury; mesenchymal stem cell; microRNA