Abstract: SA-PO305
Inhibiting Post-Translational Core Fucosylation Protects against Albumin-Induced Proximal Tubular Epithelial Cell Injury
Session Information
- Extracellular Matrix Biology, Fibrosis, Cell Adhesion
November 04, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Cell Biology
- 204 Extracellular Matrix Biology, Fibrosis, Cell Adhesion
Author
- Dapeng, Wang, The First Affiliated Hospital of Dalian Medical University, Dalian, China
Background
Albuminuria is an independent risk factor for renal interstitial fibrosis (RIF). Glomerular-filtered albumin may cause injury to proximal tubular epithelial cells (PTECs) in endocytic and non-endocytic pathways via megalin and TGFβRII respectively. As megalin and TGFβRII are both modified by post-translational core fucosylation which plays a critical role in RIF, we identified whether or not core fucosylation is a potential target for reducing albumin-induced injury to PTECs.
Methods
We constructed a human PTEC-derived cell line of HK-2 cells and a bovine serum albumin (BSA) injury model in vitro. RNAi was used to inhibit expression of megalin, TGFβRII and FUT8. Western blotting, immunostaining, enzyme-linked immunosorbent assay, lectin blotting and fluorescence-activated cell sorting were used to determine BSA-induced endocytic and non-endocytic damages in HK-2 cells. FUT8 is a core fucosylation-related gene, the expression of FUT8 was significantly increased after incubation with BSA in HK-2 cells.
Results
FUT8siRNA significantly reduced core fucosyaltion of megalin and TGFβRII. Meanwhile, it could also inhibit activation of the TGFβ/TGFβRII/Smad2/3 signaling pathway. Furthermore, FUT8siRNA could reduce monocyte chemotactic protein-1; reactive oxygen species and apoptosis; and significantly decrease fibronectin and collagen I levels in BSA-overloaded HK-2 cells. Notably, inhibiting core fucosylation is more effective than either inhibiting megalin or inhibiting TGFβRII in the prevention of albumin-induced injury to PTECs.
Conclusion
Inhibition of core fucosylation could effectively alleviate albumin-induced endocytic and non-endocytic injury to PTECs, our study provides a potential therapeutic target in albuminuria-induced injury.
Funding
- Government Support - Non-U.S.