Possible role of NFĸB in the embryonic vascular remodeling and the endothelial-mesenchymal transition process

Abstract

The NFκB family of transcription factors, particularly the activated p50/p65 heterodimer, is expressed in vascular cells during intimal thickening formation when hemodynamic conditions are altered. Here, we report that p50, p65, IκBα and IKKα display different spatial and temporal patterns of expression and distribution during both chicken embryo aortic wall remodeling and intimal thickening development. Additionally, we show that both p50 and p65 were located in the nucleus of some mesenchymal cells expressing α-smooth muscle actin which are present in the spontaneous intimal thickening observed at embryonic days 12-14 of development. We also demonstrated that both NFκB subunits are present in monolayers of primary embryonic aortic endothelial cells attached to fibronectin and stimulated with complete medium. This study demonstrates for the first time the presence of activated NFκB during the remodeling of the embryonic aortic wall and the formation of intimal thickening, providing evidence that suggest a possible role for this transcription factor in the EndoMT process.

Potential role of the Jagged1/Notch1 signaling pathway in the endothelial‐myofibroblast transition during BLM‐induced pulmonary fibrosis

“…In conclusion, during the early stages of BLM‐induced pulmonary fibrosis, excessive secretion of some cytokines (e.g., TNF‐α) promotes the increased transcription of Jagged1 and consequently activates the Jagged1/Notch1 signaling pathway in PMVECs (Benedito et al, ; Sainson et al, ), promoting the progression of Endo‐MT. Moreover, common stimuli (e.g., TNF‐α and hypoxia) can also lead to the rapid activation and translocation of NF‐κB (Ang & Tergaonkar, ; Arciniegas, Carrillo, De Sanctis, & Candelle, ). Active NF‐κB may be involved in the process of Jagged1‐induced α‐SMA expression in PMVECs by a “non‐canonical” pathway (Arciniegas et al, ).…”

“…Moreover, common stimuli (e.g., TNF‐α and hypoxia) can also lead to the rapid activation and translocation of NF‐κB (Ang & Tergaonkar, ; Arciniegas, Carrillo, De Sanctis, & Candelle, ). Active NF‐κB may be involved in the process of Jagged1‐induced α‐SMA expression in PMVECs by a “non‐canonical” pathway (Arciniegas et al, ). This pathway is different from canonical Notch signaling which regulates α‐SMA expression via CSL or HRT in smooth muscle cells and mesenchymal fibroblasts (Doi et al, ; Morrow et al, ; Noseda et al, ; Ono, Sensui, Okutsu, & Nagatomi, ; Proweller, Pear, & Parmacek, ).…”

Nur77 deficiency exacerbates cardiac fibrosis after myocardial infarction by promoting endothelial‐to‐mesenchymal transition

“…The molecular mechanisms of how Nur77 regulates EndMT are unclear. Activation and nuclear translocation of the NF‐κB transcription factor is a key step in inflammation‐mediated EndMT, as activated NF‐κB was observed in cells undergoing EndMT in embryogenesis, intima‐thickening, and also in aged endothelial cells, embryonic and adult valve endothelial cells (Arciniegas, Carrillo, de Sanctis, & Candelle, 2008; Fleenor, Marshall, Rippe, & Seals, 2012; Mahler, Farrar, & Butcher, 2013). A previous study has shown the induction of EndMT with IL‐1β and TGFβ2 resulted in increased translocation of p65 to the nucleus and blocking of NF‐κB activity led to inhibition of EndMT (Maleszewska et al, 2013).…”

NF‐κBP65 promotes invasion and metastasis of oesophageal squamous cell cancer by regulating matrix metalloproteinase‐9 and epithelial‐to‐mesenchymal transition

“…The tumour suppressor protein, N‐myc downstream‐regulated gene 2 (NDRG2), suppresses fibrosarcoma and melanoma cell invasion by suppressing NF‐κB‐mediated MMP‐9 and MMP‐2 expression and activity (Kim et al, ). Ranpirnase has an inhibitory effect on NF‐κB by suppressing its nuclear translocation; mesothelioma cells treated by ranpirnase have strongly reduced MMP9 activity, an effect that is specifically induced by TNF‐α‐mediated activation of NF‐κB (Arciniegas et al, ). Epithelial–mesenchymal transition (EMT), a critical step in tumour cell invasion and metastasis, is enhanced by NF‐κB.…”