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.

IL-1β–Primed Mesenchymal Stromal Cells Improve Epidermal Substitute Engraftment and Wound Healing via Matrix Metalloproteinases and Transforming Growth Factor-β1

“…However, several other molecular pathways may be worth exploring, such as mitogen-activated protein kinase, protein kinase B, integrin, and Wnt/b-catenin (Longmate and Dipersio, 2014;Park et al, 2018). Importantly, previous works have shown that IL-1b could activate the Wnt/b-catenin pathway, resulting in more angiogenesis (Sun et al, 2016) and increased production of MMPs (Ge et al, 2009). This signaling pathway was also shown to promote cell migration in a model of burn wound through the release of Wnt4-carrying exosomes (Zhang et al, 2015a(Zhang et al, , 2015b.…”

Interleukin‐1β augments the angiogenesis of endothelial progenitor cells in an NF‐κB/CXCR7‐dependent manner

“…These results indicate that CXCR7 plays a critical role in IL-1β-induced EPC angiogenesis, which is consistent with the findings of Watanabe, K. and colleagues in HUVECs. 40 NF-κB is a classical IL-1β-induced downstream signalling molecule that plays critical roles in IL-1β-induced angiogenesis in mesenchymal stromal cells 41 and angiogenic factor expression in temporomandibular disc cells. 34 Moreover, NF-κB and G protein-coupled receptors are closely connected in inflammation and tumorigenesis.…”

Cancer-associated fibroblasts promote cell proliferation and invasion via paracrine Wnt/IL1β signaling pathway in human bladder cancer

“…We then investigated whether the accumulation of IL1 is correlated with activation of Wnt signaling pathways. Several studies suggest that IL1 could enhance Wnt signal via inhibiting DKK1 or indirectly interacting with intracellular NF-kB and CREB signaling [12,13,22]. Based on these findings, we treated T24 cells with recombinant IL1 , and showed remarkably up-regulated expression of Wnt targets.…”