Abstract: TH-PO0219
Palmitoyltransferase DHHC9 Inhibits Macrophage TSP1 Secretion and Suppresses Renal Fibrosis
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
- Fu, Shiyu, Center for Kidney Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Gu, Mengru, Center for Kidney Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Ren, Yizhi, Center for Kidney Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Jiang, Hanlu, Center for Kidney Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Li, Ying, Center for Kidney Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Dai, Chunsun, Center for Kidney Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
Background
As chronic kidney disease (CKD) progresses, renal fibrotic lesions develop, accompanied by persistent accumulation of inflammatory cells, particularly macrophages, in kidney tissue. While DHHC9 has been implicated in regulating renal fibrosis in tubular cells, its function in macrophages remains unknown. Thrombospondin-1 (TSP1), a glycoprotein produced by various nucleated cells, promotes renal fibrosis by stimulating matrix production and activating TGF-β1. Accordingly, we hypothesized that macrophage DHHC9 may influence CKD progression by modulating TSP1 secretion.
Methods
Macrophage-specific DHHC9 knockout mice were generated using the Cre/LoxP system. Renal fibrosis was induced by ischemia-reperfusion injury (IRI) or unilateral ureteral obstruction (UUO). Bone marrow-derived macrophages (BMDMs) were treated with TGF-β1. S-palmitoylation of TSP1 was assessed using an acyl-biotin exchange assay.
Results
DHHC9 expression was significantly downregulated in macrophages within fibrotic kidneys. Macrophage-specific deletion of DHHC9 increased extracellular matrix (ECM) production and exacerbated IRI- or UUO-induced renal fibrosis. Mechanistically, DHHC9 catalyzed palmitoylation of TSP1 at the Cys16 site, which was critical for inhibiting TSP1 secretion from macrophages. Reduced TSP1 secretion subsequently decreased fibroblast activation and ECM production.
Conclusion
This study demonstrates that DHHC9-mediated palmitoylation of TSP1 in macrophages suppresses TSP1 secretion and plays a protective role against renal fibrosis. Targeting the DHHC9-TSP1 axis in macrophages may represent a novel therapeutic strategy for CKD.
Funding
- Government Support – Non-U.S.