Abstract: FR-PO1213
Furin Activity Is Decreased in CKD Mouse Model
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
- Ramos, Everly, Mass General Brigham Inc, Boston, Massachusetts, United States
- Xie, Han, Massachusetts General Hospital, Boston, Massachusetts, United States
- Fan, Yu, Massachusetts General Hospital, Boston, Massachusetts, United States
- Rhee, Eugene P., Massachusetts General Hospital, Boston, Massachusetts, United States
- Simic, Petra, Massachusetts General Hospital, Boston, Massachusetts, United States
Background
Furin, a ubiquitous proprotein convertase, activates precursor proteins by cleaving at the canonical Arg-X-Lys-Arg↓ motif and processes intact fibroblast growth factor-23 (iFGF23) into inactive N- and C-terminal fragments (cFGF23). iFGF23 regulates bone and mineral metabolism, predicts left ventricular hypertrophy, chronic kidney disease (CKD progression) and higher mortality in dialysis patients. Furin activity in CKD has not been evaluated.
Methods
We examined how CKD alters furin using an adenine-induced CKD model in wild-type C57BL/6J mice. Animals received adenine-enriched chow for four weeks. The degree of proteolytic cleavage was quantified by the relative abundance of iFGF23 and cFGF23 cleavage fragments in circulation, utilizing ELISAs that specifically detect only iFGF23 or a combination of iFGF23 and cFGF23 fragments. Measurements of furin activity, plasma concentration and renal furin expression were taken at baseline and at four weeks.
Results
FGF23 cleavage was decreased in CKD as shown by reduction of plasma cFGF23/iFGF23 ratio (Fig 1A). Fluorogenic substrate assay (Fig 1B) showed a reduction in plasma furin activity, while circulating furin protein remained unchanged (Fig 1C). In kidney lysates, enzymatic activity did not differ (Figure 1D), yet immunoblotting demonstrated increased furin abundance (Fig 2). Immunofluorsecence also showed increased protein expression predominantly along the basolateral membrane of proximal tubular epithelial cells.
Conclusion
In CKD mice, plasma furin activity and FGF23 cleavage are decreased, while kidney tissue expression of furin is increased. Further research into the mechanism of decreased furin activity in CKD is needed.
Funding
- Private Foundation Support