Abstract: FR-PO935
TLR4-Myd88-NF-κβ and Calcineurin/NFAT Signaling Pathway Cooperatively Regulate Lipopolysaccharide-Induced Angptl4 in Podocyte
Session Information
- Glomerular Diseases: Podocyte Biology - II
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1204 Podocyte Biology
Author
- Shen, Xiujin, The First Affiliated Hospitial, Zhejiang University, Hangzhou, China
Background
Inflammation and immunological abnormalities damage podocytes and induce proteinuria. Angptl4 is a member of the angiopoietin-like protein family, which is involved in lipid metabolism, wound repair, tumor metastasis . Podocyte Angptl4 is involved in proteinuria formation, but its upstream regulation mechanism is still unclear. This study aims to clarify the molecular mechanisms involved in Angptl4 expression
Methods
LPS induced podocyte injury model was used to clarify the effect of LPS on Angptl4 in podocytes . Then, the effect of TLR4-Myd88- NF-κβ signaling pathway on Angptl4 expression was detected. In addition, Calcineurin inhibitors were used to detect Angptl4 expression in LPS-induced MCD model. Podocytes was transfected with Angptl4 to investigate the role of Angptl4 on podocyte injury.
Results
Angptl4 was promoted after LPS induction. Angptl4 overexpression disordered podocyte cytoskeleton, reduced synaptopodin , which was further decreased by LPS induction, while Angptl4 knockdown partially restored synaptoodin and podocyte cytoskeleton in LPS induced podocytes. In addition, TLR4 ,Myd88 siRNA and NF-κβ inhibitor PDTC effectively inhibited Angptl4 after LPS induction, while CD14 siRNA had no effect on Angptl4 expression, implying that Angptl4 was regulated by TLR4-Myd88-NF-κβ pathway. Furthermore, Calcineurin inhibitors significantly inhibited Angptl4, reduced the nuclear translocation of NFATc1, and restored podocyte cytoskeleton, which suggested that CaN inhibitors affected the expression of Angptl4 also through Calcineurin-NFAT signaling pathway.
Conclusion
LPS induced Angptl4 was regulated by Calcineurin-NFAT and TLR4-Myd88-NF-KB signaling pathway in podocytes
TLR4-Myd88-NF-κβ and Calcineurin/NFAT signaling pathway cooperatively regulate LPS induced Angptl4 in podocyte
Funding
- Government Support - Non-U.S.