High glucose aggravates lipid deposition in glomerular endothelial cells by LXRs/LncRNAOR13C9/ABCA1 pathway

Abstract

Background Lipid metabolism disorder is closely related to diabetic nephropathy (DN), but the mechanism remains unclear. The aim of this study was to investigate the effect of high glucose on intracellular accumulation of lipids and to clarify the possible mechanism. Methods We found that in human glomerular endothelial cells (GEnCs), cholesterol could reduce cell activity, lead to abnormal lipid deposition in cells and high glucose can aggravate lipid deposition under high cholesterol load. Results CCK8 showed that soluble cholesterol could reduce GEnCs cells activity. Oil red O staining and cholesterol quantification experiment showed that the intracellular lipid deposition did not obvious after the intervention of high glucose (HG), but the intracellular lipid deposition increased under HG combined with high cholesterol (HC). The results of RT-qPCR,WB and immunofluorescence experiment showed the expression of ABCA1 in HC group increased significantly. However, compared with the HC group, the expression of ABCA1in the HG and HC group were decreased. And then we found HG affected ABCA1 up-regulation by LXRs. Based on Gene Microarray, we found that LXRs regulation of ABCA1 transcription requires the involvement of LncRNAOR13C9. Conclusions HG could enhance intracellular lipid deposition by interfering with cellular response to HC to up-regulate the expression of ABCA1, and HG blocked the expression of ABCA1 by down-regulating LXRs, and LncRNAOR13C9 also played an important role in this process. It further elucidate the pathogenesis of DN and provide a new target for the prevention and treatment of DN.

High Glucose Aggravates Cholesterol Accumulation in Glomerular Endothelial Cells Through the LXRs/LncRNAOR13C9/ABCA1 Regulatory Network

“…This manuscript has been released as a Pre-Print at ResearchGate DOI: 10.21203/rs.3.rs-17912/v1 (Xiao et al, 2020).…”