LXR agonist T0901317 upregulates thrombomodulin expression in glomerular endothelial cells by inhibition of nuclear factor‑κB

  • Authors:
    • Hanlu Ding
    • Yi Li
    • Yunlin Feng
    • Jin Chen
    • Xiang Zhong
    • Nan Wang
    • Wei Wang
    • Ping Zhang
    • Li Wang
  • View Affiliations

  • Published online on: April 15, 2016     https://doi.org/10.3892/mmr.2016.5138
  • Pages: 4888-4896
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Abstract

Dysfunction of glomerular endothelial cells (GECs) induces a variety of symptoms, including proteinuria, inflammation, vascular diseases, fibrosis and thrombosis. Thrombomodulin (TM) acts as a vasoprotective molecule on the surface of the vascular endothelial cells to maintain the homeostasis of the endothelial microenvironment by suppressing cellular proliferation, adhesion and inflammatory responses. Liver X receptor (LXR), a nuclear receptor (NR) and a bile acid‑activated transcription factor, regulates metabolism and cholesterol transport, vascular tension and inflammation. Previous studies indicated that TM expression is upregulated by various NRs; however, it is unclear whether pharmacological modulation of LXR may affect TM expression and GEC function. The current study revealed that LXR activation by its agonist, T0901317, upregulates the expression and activity of TM. This effect was mediated specifically through LXR‑α, and not through LXR‑β. Additionally, T0901317 treatment inhibited nuclear factor‑κB (NF‑κB) signaling and the secretion of high glucose‑induced proinflammatory mediators, including tumor necrosis factor‑α and interleukin‑1β in GECs. Co‑immunoprecipitation experiments determined that treatment with T0901317 enhances the interaction between LXR‑α and the transcriptional coactivator, p300, in GEC extracts. The present findings suggest that NF‑κB may be a negative regulator of TM expression, and its removal may contribute to TM gene expression, particularly when in competition with the T0901317‑enhanced formation of the LXR/p300 complex. Therefore, LXR may be a novel molecular target for manipulating TM in GECs, which may advance the treatment of endothelial cell‑associated diseases.
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June-2016
Volume 13 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Ding H, Li Y, Feng Y, Chen J, Zhong X, Wang N, Wang W, Zhang P and Wang L: LXR agonist T0901317 upregulates thrombomodulin expression in glomerular endothelial cells by inhibition of nuclear factor‑κB. Mol Med Rep 13: 4888-4896, 2016
APA
Ding, H., Li, Y., Feng, Y., Chen, J., Zhong, X., Wang, N. ... Wang, L. (2016). LXR agonist T0901317 upregulates thrombomodulin expression in glomerular endothelial cells by inhibition of nuclear factor‑κB. Molecular Medicine Reports, 13, 4888-4896. https://doi.org/10.3892/mmr.2016.5138
MLA
Ding, H., Li, Y., Feng, Y., Chen, J., Zhong, X., Wang, N., Wang, W., Zhang, P., Wang, L."LXR agonist T0901317 upregulates thrombomodulin expression in glomerular endothelial cells by inhibition of nuclear factor‑κB". Molecular Medicine Reports 13.6 (2016): 4888-4896.
Chicago
Ding, H., Li, Y., Feng, Y., Chen, J., Zhong, X., Wang, N., Wang, W., Zhang, P., Wang, L."LXR agonist T0901317 upregulates thrombomodulin expression in glomerular endothelial cells by inhibition of nuclear factor‑κB". Molecular Medicine Reports 13, no. 6 (2016): 4888-4896. https://doi.org/10.3892/mmr.2016.5138