Abstract: SA-OR021
JNK-Associated Leucine Zipper Protein Protects Intimal Hyperplasia and Mitigates Arteriovenous Fistula (AVF) Dysfunction by Regulating the TGF-β1/Smad Signaling Pathway
Session Information
- Dialysis Vascular Access: From Basic Discovery to Translational Science
November 08, 2025 | Location: Room 342D, Convention Center
Abstract Time: 04:50 PM - 05:00 PM
Category: Dialysis
- 803 Dialysis: Vascular Access
Authors
- He, Qunpeng, Renmin Hospital of Wuhan University, Wuhan, China
- Zhang, Lu, Renmin Hospital of Wuhan University, Wuhan, China
- Tian, Maoqing, Renmin Hospital of Wuhan University, Wuhan, China
- Wang, Huiming, Renmin Hospital of Wuhan University, Wuhan, China
Background
Observation of JLP expression in AVF vessels and its effects on VSMCs proliferation, migration, and neointimal formation.
Methods
Observe the role of JLP in the neointimal hyperplasia at the venous end of AVF models in WT mice, JLP knockout mice, and VSMC specific reporting mice. Mice primary VSMCs were used for in vitro experiments, and the cells were divided into control group, JLP KO group, negative control+TGF-β1 stimulation group, and JLP KO+TGF-β1 group. WB and IF assay was used to detect the expression of JLP, TGF-β1, SMA, OPN, PCNA, p38 MAPK, and pSmad2/3 in each group of cells.
Results
This study found JLP expression in human and mice blood vessels. The expression level of JLP in the dysfunction AVF segment was significantly downregulated compared to the control(P<0.05). 28 days after AVF, the level of JLP protein in blood vessels was significantly downregulated compared to control blood vessels (P<0.05). JLP KO mice showed more significant intimal hyperplasia and significantly reduced luminal area in the AVF vein segment after AVF surgery compared to WT mice. Using VSMC specific reporting mice, we found that the majority of AVF neointimal cells were derived from dedifferentiated VSMCs, and the expression level of JLP in these cells was significantly downregulated. In vitro cell experiments showed a downregulation of JLP protein expression in the TGF-β1 group compared to the Ctrl(P<0.05); Compared with the TGF-β1 group, the jlp-shRNA+TGFβ-1 group showed a significant upregulation of TGF-β1, OPN, p38 MAPK, and pSmad2/3 protein expression. The downregulation of JLP function in AVF vessels promotes the migration, proliferation, and secretion of extracellular matrix by VSMCs. The decreased expression of JLP activates the TGF-β1 signaling pathway.
Conclusion
JLP is induced by TGF-β1 and restricts the dedifferentiation, proliferation, and migration of vascular smooth muscle cells through negative feedback regulation of the TGF -β pathway, thereby limiting vascular fibrosis response.
Funding
- Government Support – Non-U.S.