Abstract
The pathogenesis of IgA nephropathy (IgAN) is still unknown, but reportedly, interleukin 6 (IL-6) is involved in this process. However, its role in damaging glomerular endothelial cells is still unclear. Therefore, in this study, to clarify the mechanism of the pathogenesis of IgAN, we investigated the effect of IL-6 on the permeability of glomerular endothelial cells. A rat model of IgAN was established, and the animals divided into two groups, namely, the normal and IgAN groups. Glomerular endothelial cell injury was evaluated via electron microscopy. Furthermore, IL-6-induced changes in the permeability of human renal glomerular endothelial cells (HRGECs) were measured via trans-endothelial resistance (TEER) measurements and fluorescein isothiocyanate-dextran fluorescence. Furthermore, vascular endothelial-cadherin (VE-cadherin) was overexpressed to clarify the effect of IL-6 on HRGEC permeability, and to determine the pathway by which it acts. The classical signaling pathway was blocked by silencing IL-6R and the trans-signaling pathway was blocked by sgp30Fc. In IgAN rats, electron microscopy showed glomerular endothelial cell damage and western blotting revealed a significant increase in IL-6 expression, while VE-cadherin expression decreased significantly in the renal tissues. IL-6/IL-6R stimulation also significantly increased the permeability of HRGECs (p < 0.05). This effect was significantly reduced by VE-cadherin overexpression (p < 0.01). After IL-6R was silenced, IL-6/IL-6R still significantly reduced VE-cadherin expression and sgp30Fc blocked the trans-signaling pathway as well as the upregulation of IL-6/IL-6R-induced VE-cadherin expression. This suggests that IL-6 mainly acts via the trans-signaling pathway. IL-6 increased the permeability of HRGECs by decreasing the expression of VE-cadherin via the trans-signaling pathway.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.