| Author |
Wang, Li Chen, Jin Wang, Nan Wang, Wei Zhong, Xiang Feng, Yunlin Ding, Hanlu Li, Yi Zhang, Ping |
| Description |
Author Affiliation: Ding H ( Department of Nephrology, University of Electronic Science and Technology, Sichuan Academy of Sciences, Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.); Li Y ( Department of Nephrology, University of Electronic Science and Technology, Sichuan Academy of Sciences, Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.); Feng Y ( Department of Nephrology, University of Electronic Science and Technology, Sichuan Academy of Sciences, Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.); Chen J ( Department of Nephrology, University of Electronic Science and Technology, Sichuan Academy of Sciences, Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.); Zhong X ( Department of Nephrology, University of Electronic Science and Technology, Sichuan Academy of Sciences, Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.); Wang N ( Department of Nephrology, Chengdu Second People's Hospital, Chengdu, Sichuan 610041, P.R. China.); Wang W ( Department of Nephrology, University of Electronic Science and Technology, Sichuan Academy of Sciences, Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.); Zhang P ( Department of Nephrology, University of Electronic Science and Technology, Sichuan Academy of Sciences, Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.); Wang L ( Department of Nephrology, University of Electronic Science and Technology, Sichuan Academy of Sciences, Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.) |
| 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 acidactivated 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 , and not through LXRß. Additionally, T0901317 treatment inhibited nuclear factorκB (NFκB) signaling and the secretion of high glucoseinduced proinflammatory mediators, including tumor necrosis factor and interleukin1ß in GECs. Coimmunoprecipitation experiments determined that treatment with T0901317 enhances the interaction between LXR and the transcriptional coactivator, p300, in GEC extracts. The present findings suggest that NFκB may be a negative regulator of TM expression, and its removal may contribute to TM gene expression, particularly when in competition with the T0901317enhanced 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 cellassociated diseases. |
