Kidney Week

Abstract: TH-PO0271

Complement Factor D in Mesangial Cells Contributes to Sclerotic Remodeling in FSGS

Session Information

• Glomerular Diseases: Cell Biology
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Iwamoto, Takaki, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Takaki Iwamoto, MD

• Nakano, Toshiaki, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Toshiaki Nakano, MD, PhD

• Torisu, Kumiko, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Kumiko Torisu, MD, PhD

• Hayashi, Sahomi, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Sahomi Hayashi, MD, PhD

• Yamada, Shunsuke, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Shunsuke Yamada, MD, PhD

• Ago, Tetsuro, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Tetsuro Ago, MD, PhD

Background

Focal Segmental Glomerulosclerosis (FSGS) is one of the major causes of nephrotic syndrome characterized by severe proteinuria and is a refractory kidney disease with a poor prognosis, as a substantial proportion of patients progress to end-stage renal disease. Recent studies suggest that the progression of FSGS is not limited to podocyte injury but also involves disruption of intercellular crosstalk within the glomerulus. Our previous omics analysis showed that complement factor D (CFD) was significantly elevated in FSGS compared with transplant donor kidneys. We therefore investigated whether CFD contributes to FSGS progression.

Methods

Glomerular localization of CFD was analyzed by immunostaining of human renal biopsy specimens. An BALB/c mouse model of Focal Segmental Glomerulosclerosis was established by administering Adriamycin (15 mg/kg), and changes in CFD expression were evaluated by western blotting and immunostaining, along with their association with glomerulosclerosis. Furthermore, using a mouse mesangial cell line (MES13), fibrosis in CFD knockdown cells was analyzed by western blotting and immunostaining.

Results

In healthy adults, no CFD immunostaining signal was detected within the glomeruli; however, in FSGS, CFD expression was upregulated and co-localized with platelet-derived growth factor receptor beta (PDGFR-β) and integrin α8, suggesting increased CFD expression in mesangial cells. Although CFD signals in renal tubular cells tended to be higher in FSGS than in healthy controls, the difference was not statistically significant. In the kidneys of an FSGS model BALB/c mouse, CFD expression was markedly increased, particularly in PDGFR-β- and integrin α8-positive mesangial cells within the glomeruli. CFD immunostaining signal was also observed in areas positive for fibronectin within the glomeruli. In MES13 cells, treatment with Adriamycin increased both fibronectin and CFD expression. Subsequently, CFD knockdown cells were generated, and reduced CFD expression was confirmed by immunostaining. In these cells, ADR-induced fibronectin upregulation was suppressed.

Conclusion

CFD is suggested to contribute to glomerulosclerosis in FSGS through the promotion of mesangial cell fibrosis.