Kidney Week

Abstract: TH-PO0238

Depalmitoylase ABHD17B Promotes Vascular Smooth Muscle Cell Calcification in CKD Through Interaction with BRG1

Session Information

• CKD: Mechanisms of Injury and Fibrosis - 1
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2203 CKD (Non-Dialysis): Mechanisms

Authors

• Li, Yi, Department of Nephrology and Institute of Nephrology, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Sichuan Clinical Research Centre for Kidney Diseases, Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Chengdu, China

Yi Li

• Li, Guisen, Department of Nephrology and Institute of Nephrology, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Sichuan Clinical Research Centre for Kidney Diseases, Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Chengdu, China

Guisen Li, MD, PhD

• Wang, Li, Department of Nephrology and Institute of Nephrology, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Sichuan Clinical Research Centre for Kidney Diseases, Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Chengdu, China

Li Wang, MD, PhD

Background

Vascular calcification is a common and severe complication of chronic kidney disease (CKD), with osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) playing a central role in its pathogenesis. Although S-palmitoylation has been implicated in osteoblast differentiation and atherosclerosis, its role in CKD-associated vascular calcification remains unexplored. This study aimed to investigate the role of S-palmitoylation and its key regulatory molecules in this process.

Methods

A CKD vascular calcification model was established in rats via 5/6 nephrectomy combined with a high-phosphorus diet. In vitro calcification and osteogenic transdifferentiation of VSMCs were induced using β-glycerophosphate and CaCl₂. VSMCs were treated with palmitoylation inhibitor 2-BP and depalmitoylation inhibitor Palm-B. DIA-based quantitative proteomics identified ABHD17B as a key depalmitoylase target. ABHD17B expression was subsequently examined in aortic tissues from CKD rats and hemodialysis patients. Gain- and loss-of-function experiments, molecular docking, and immunoprecipitation were performed to elucidate underlying mechanisms.

Results

Under calcifying conditions, calcification and osteogenic transdifferentiation of VSMCs were exacerbated by 2-BP and inhibited by Palm-B treatment. The expression of ABHD17B was increased in calcified VSMCs and calcified arteries in rat underwent 5/6 nephrectomy combined with a high-phosphorus diet, as well as calcified arteries from patients with hemodialysis presenting vascular calcification. Importantly, silencing ABHD17B expression inhibited VSMCs calcification and osteogenic transdifferentiation, whereas transfection of plasmids expressing ABHD17B promoted calcification of VSMCs. Mechanistically, the Cys1205 residue of Brahma related gene 1 (BRG1) can undergo S-palmitoylation modification. ABHD17B interacted with BRG1 and synergistically promote VSMCs calcification. Interestingly, the Cys1205 residue of BRG1 is involved in the interaction between ABHD17 and BRG1 and affects its synergistic pro-calcification effect on VSMCs.

Conclusion

S-palmitoylation modification is closely associated with vascular calcification in CKD, and ABHD17B might be a novel potential target for the prevention and treatment of vascular calcification in CKD.

Funding

• Government Support – Non-U.S.