Abstract: FR-PO1222
COMMD5 Inhibits Vascular Calcification in CKD by Promoting Lysosomal Degradation of RUNX2 via Cytoskeletal Stabilization
Session Information
- CKD: Mechanisms, AKI, and Beyond - 2
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Dong, Xiaoying, South China University of Technology, Guangzhou, Guangdong, China
- Liu, Shuangxin, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
- Zhao, Zewen, South China University of Technology, Guangzhou, Guangdong, China
Background
Vascular calcification (VC) is a highly prevalent and life-threatening complication of chronic kidney disease (CKD), contributing to increased cardiovascular morbidity and mortality.Although the underlying mechanisms remain unclear, previous studies have reported that osteogenic transdifferentiation of Vascular Smooth Muscle Cells (VSMCs) participates in VC progression.COMMD5/HCaRG is a hypertension-related, calcium-regulated gene, and is also involved in kidney repair, tumor inhibition and hypotensive effects. We aim to probe into the exact role and molecular mechanism of COMMD5 in VC in patients with CKD.
Methods
1.ELISA was used to measure patients' serum.
2.Assessment of aortic arch calcification score of patients.
3.Immunohistochemistry and Immunofluorescence staining was used to detect the expression of COMMD5 in VC tissues.
4.COMMD5-transgenic mice (COMMD5-Tg) and VSMC-specific COMMD5 knockin mice (COMMD5-TagIn) were constrcted.
5.Human aortic vascular smooth muscle cells were cultivated and were induced to calcify.
6.Von Kossa assay and Alizarin red staining were used to examine calcification.
7.Western blot analysis were used to quantify protein.
8.All analyses were performed with SPSS 23.0 software, and two-tailed P < 0.05 was considered statistically significant.
9.The protocol for clinical study conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Ethics Committee.
Results
1.Serum COMMD5 levels is markedly decreased with increasing aortic arch calcification score of patients with CKD and VC.
2.The expression of COMMD5 in calcified tissues of human and mice decreased.
3.COMMD5 prevented VSMCs from osteogenic transdifferentiation by promoting the degradation of RUNX2, which played a significant role in VC.
4.COMMD5 ensured the normal degradation of RUNX2 by lysosomes by maintaining the stability of the cytoskeleton.
Conclusion
COMMD5 prevent VC by inhibiting the osteogenic transdifferentiation of VSMCs, and may serve as a potential therapeutic target for VC.
Funding
- Government Support – Non-U.S.