TNFα-induced down-regulation of Sox18 in endothelial cells is dependent on NF-κB

Basílio, José; Hoeth, Martina; Holper-Schichl, Yvonne M; Resch, Ulrike; Mayer, Herbert; Hofer‐Warbinek, Renate; Martin, Rainer de

doi:10.1016/j.bbrc.2013.11.030

Cited by 8 publications

(15 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, due to the versatile roles of NF-κB in cellular processes, including inflammatory response, tumour cell proliferation, invasion, cell survival and angiogenesis (40,41), the inhibition of NF-κB as a strategy to specifically combat metastasis has certainly its limitations. It was discovered that NF-κB co-regulates the transcription factor SOX18 (24,25), which itself regulates PROX1 (9), which is 'the' marker for lymphatic vessels. This recommends these transcription factors as more specific targets for intervention, as they exhibit much more restricted expression profiles (9,10) compared with NF-κB.…”

Section: Discussionmentioning

confidence: 99%

“…12(S)-HETE reduces the resilience of the lymph endothelial barrier (4) through activation of NF-κB (26,27). Reportedly, NF-κB cross-talks to the endothelia-specific transcription factor SOX18 in human umbilical vein endothelial cells (HUVECs) (24). This prompted investigation of the expression of SOX18 in LECs upon 12(S)-HETE treatment.…”

Section: (S)-hete Induces Sox18mentioning

confidence: 99%

“…The results of the current study demonstrated that 12(S)-HETE strongly induced the expression of SOX18 and PROX1, and their inhibition attenuated CCID formation. Thus, the 12(S)-HETEtriggered signal transduction pathway, in addition to recently established cross-talk between SOX18 and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) (24,25), which also contributes to breast cancer cell intravasation (26)(27)(28), were examined.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

12(S)-HETE induces lymph endothelial cell retraction inï¿½vitro by upregulation of SOX18

et al. 2018

Self Cite

View full text Add to dashboard Cite

Metastasising breast cancer cells communicate with adjacent lymph endothelia, intravasate and disseminate through lymphatic routes, colonise lymph nodes and finally metastasize to distant organs. Thus, understanding and blocking intravasation may attenuate the metastatic cascade at an early step. As a trigger factor, which causes the retraction of lymph endothelial cells (LECs) and opens entry ports for tumour cell intravasation, MDA-MB231 breast cancer cells secrete the pro-metastatic arachidonic acid metabolite, 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid [12(S)-HETE]. In the current study, treatment of LECs with 12(S)-HETE upregulated the expression of the transcription factors SRY-related HMG-box 18 (SOX18) and prospero homeobox protein 1 (PROX1), which determine endothelial development. Thus, whether they have a role in LEC retraction was determined using a validated intravasation assay, small interfering RNA mediated knockdown of gene expression, and mRNA and protein expression analyses. Specific inhibition of SOX18 or PROX1 significantly attenuated in vitro intravasation of MDA-MB231 spheroids through the LEC barrier and 12(S)-HETE-triggered signals were transduced by the high and low affinity receptors, 12(S)-HETE receptor and leukotriene B4 receptor 2. In addition, the current findings indicate that there is crosstalk between SOX18 and nuclear factor κ-light-chain-enhancer of activated B cells, which was demonstrated to contribute to MDA-MB231/lymph endothelial intravasation. The present data demonstrate that the endothelial-specific and lymph endothelial-specific transcription factors SOX18 and PROX1 contribute to LEC retraction.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: (S)-hete Induces Sox18mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

12(S)-HETE induces lymph endothelial cell retraction inï¿½vitro by upregulation of SOX18

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…NF‐κB is a key pathway activated by TNF‐α and regulates numerous downstream inflammatory genes expression . Under normal physiological condition, NF‐κB is inhibited by physical association with its inhibitory protein, inhibitor of kappa B (IκB).…”

Section: Discussionmentioning

confidence: 99%

“…NF-kB is a key pathway activated by TNF-a and regulates numerous downstream inflammatory genes expression. 42,43 Under normal physiological condition, NF-kB is inhibited by physical association with its inhibitory protein, inhibitor of kappa B (IkB). Once stimulated, the NF-kB heterodimer is rapidly released from IkB and translocates to the nucleus, where it activates the transcription of target genes.…”

mentioning

confidence: 99%

LIM mineralization protein‐1 suppresses TNF‐α induced intervertebral disc degeneration by maintaining nucleus pulposus extracellular matrix production and inhibiting matrix metalloproteinases expression

Liu

Pan

Yang

et al. 2014

Journal Orthopaedic Research

View full text Add to dashboard Cite

Imbalanced metabolism of Nucleus pulposus (NP) extracellular matrix (ECM) is closely correlated to Intervertebral Disc Degenerative Disease. LIM mineralization protein-1 (LMP-1) has been proven to induce sulfated glycosaminoglycan (sGAG) production in NP and have an anti-inflammatory effect in pre-osteoclast. However, whether it has any effect on the NP ECM production and degradation under inflammatory stimulation has not been studied. In the current study, a TNF-a induced cell model was established in vitro. Lentivirus encoding LMP-1 (LV-LMP-1) and short heparin LMP-1 (LV-shLMP-1) were constructed to overexpress and knockdown LMP-1 expression in NP cells. LMP-1 mRNA level was regulated in a dose-dependent manner after transfection. LV-LMP-1 increased whereas LV-shLMP-1 decreased collagen II, aggrecan, versican expression, and sGAG production. LV-LMP-1 abolished while LVshLMP-1 aggravated TNF-a mediated down-regulation of the above matrix genes via ERK1/2 activation. Moreover, LV-LMP-1 abrogated TNF-a induced MMP-3 and MMP-13 expression via inhibiting p65 translocation and MMP-3 and MMP-13 promoter activity. These results indicated that LMP-1 had an ECM production maintenance effect under inflammatory stimulation. This effect was via up-regulation of matrix genes expression at least partially through ERK1/2 activation, and down-regulation of MMPs expression through NF-kB inhibition. Keywords: LIM Mineralization Protein-1; intervertebral disc degeneration; matrix metalloproteinase; extracellular matrix; NF-kB Intervertebral disc degeneration (IVDD) is a common degenerative process of the spine as aged. 1 It has been acknowledged that IVDD is one of the most important factors associated with spinal degenerative diseases including disc herniation, spinal canal stenosis, spondylolysthesis, and degenerative scoliosis. 1,2 These diseases cause back pain, radiculopathy or myelopathy, leading to disability, low health related quality of life (HRQOL), and economic losses. Conservative treatment and surgical treatments of spinal degenerative diseases in the late stage is at huge cost and result in suboptimal clinical outcomes in many situation. 1,2 Thus, early intervention to prevent the progression of IVDD, or regenerate the degenerative disc is of great necessity.Nucleus pulposus (NP) extracellular matrix (ECM) consists mainly of loosely assembled collagen type II fibers and proteoglycan (mostly aggrecan and versican), which enable the nucleus pulposus to retain water, thereby cushioning and absorbing the considerable loads placed on the tissue. 3 IVDD is believed to be, in part, the result of imbalance between anabolism and catabolism of ECM. 4 MMPs play a central role in the disc degeneration mainly by cleaving collagens and aggrecan in NP ECM, resulting in the loss of normal disc function. 5-10 Inflammatory cytokines, which are proven to highly express in degenerative IVD, can increase MMPs expression and related ECM degradation. 11,12 As pathophysiological mechanism of IVDD has been better delineated, grow...

show abstract

Non-coding RNAs Related to Atherosclerosis

Holvoet

2021

Non-Coding RNAs at the Cross-Road of Cardiometabolic Diseases and Cancer

View full text Add to dashboard Cite

TNFα-induced down-regulation of Sox18 in endothelial cells is dependent on NF-κB

Cited by 8 publications

References 28 publications

12(S)-HETE induces lymph endothelial cell retraction inï¿½vitro by upregulation of SOX18

12(S)-HETE induces lymph endothelial cell retraction inï¿½vitro by upregulation of SOX18

LIM mineralization protein‐1 suppresses TNF‐α induced intervertebral disc degeneration by maintaining nucleus pulposus extracellular matrix production and inhibiting matrix metalloproteinases expression

Non-coding RNAs Related to Atherosclerosis

Contact Info

Product

Resources

About