ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO935

TLR4-Myd88-NF-κβ and Calcineurin/NFAT Signaling Pathway Cooperatively Regulate Lipopolysaccharide-Induced Angptl4 in Podocyte

Session Information

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.