Abstract: SA-PO753
Improvement of the Effect of HIF-1α Stabilizer on the Destruction of Tight Junctions in Intestinal Epithelial Cells Induced by Homocysteine
Session Information
- CKD: Mechanisms - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Liu, Hua, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Chen, Lei, Xi'an Jiaotong University, Xi'an, China
- Liang, Shanshan, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Xue, Jinhong, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Jiang, Hongli, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
Background
Based on previous findings that homocysteine (Hcy) can increase the permeability of intestinal epithelial Caco2 cell and lead to decreased expression of tight junction molecules, the role of HIF-1α in intestinal barrier dysfunction caused by homocysteine and the mechanism of intervention of HIF-1α stabilizer (FG-4592) on these effects were explored.
Methods
Caco2 cells was cultured and divided into four groups: normal control group, FG4592 group, homocysteine group (Hcy group), Hcy+FG4592 group. mRNA and protein expression levels of HIF-1α, ZO-1, claudin-1, occludin were detected by RT-qPCR and Western blotting. The expression level of miR-223 was detected by RT-qPCR.
Results
Hcy (0.5 mM) can reduce the expression of HIF-1α, claudin-1, occludin and ZO-1mRNA and protein in Caco2 cells, and FG-4592 can improve the expression of these induced by Hcy (P<0.05) through the RT-qPCR or Western bloting method (Fig.1). Hcy can reduce the expression of miR-223 mRNA (P<0.05), while the FG-4592 can increase the expression of miR-223 mRNA (P<0.05) (Fig.2).
Conclusion
miR-223 may be involved in the maintenance of intestinal epithelial barrier function in the experiment of using uremic serum to stimulate Caco2 cells. HIF-1α stabilizer can improve the Hcy-induced reduction expression of HIF-1α, ZO-1, claudin-1, Occludin, up-regulate the expression of miR-223 and down-regulate the expression of NLRP3, the mechanism may involve the mir-223/NLRP3 pathway.