Kidney Week

Abstract: TH-PO0257

Roxadustat-Preconditioned Mesenchymal Stem Cells Ameliorate Kidney Inflammation and Fibrosis Through STC1-Mediated NF-κB/NLRP3 Suppression

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

• Oda, Ayaka, Hiroshima Daigaku Byoin, Hiroshima, Hiroshima Prefecture, Japan

Ayaka Oda, MD

• Ishiuchi, Naoki, Hiroshima Daigaku Byoin, Hiroshima, Hiroshima Prefecture, Japan

Naoki Ishiuchi, DrMed

• Yoshida, Maria, Hiroshima Daigaku Byoin, Hiroshima, Hiroshima Prefecture, Japan

Maria Yoshida, MD

• Osaki, Yosuke, Hiroshima Daigaku Byoin, Hiroshima, Hiroshima Prefecture, Japan

Yosuke Osaki, MD, PhD

• Okubo, Aiko, Hiroshima Daigaku Byoin, Hiroshima, Hiroshima Prefecture, Japan

Aiko Okubo, MD, PhD

• Maeoka, Yujiro, Hiroshima Daigaku Byoin, Hiroshima, Hiroshima Prefecture, Japan

Yujiro Maeoka, MD, PhD

• Sasaki, Kensuke, Hiroshima Daigaku Byoin, Hiroshima, Hiroshima Prefecture, Japan

Kensuke Sasaki, MD, PhD

• Masaki, Takao, Hiroshima Daigaku Byoin, Hiroshima, Hiroshima Prefecture, Japan

Takao Masaki, MD, PhD

Background

Mesenchymal stem cells (MSCs) have emerged as a promising cell-based therapy for kidney disease due to their anti-inflammatory and anti-fibrotic effects. We have previously demonstrated that hypoxic preconditioning enhances the anti-inflammatory and anti-fibrotic effects of MSCs in kidney injury. Here, we investigated whether pharmacological preconditioning with roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, enhances the therapeutic efficacy of MSCs in a rat model of renal ischemia-reperfusion injury (IRI) and explored the underlying mechanisms.

Methods

A rat renal IRI model was established by clamping the left renal artery for 60 minutes. MSCs cultured with or without roxadustat (HIF-MSCs and untreated MSCs, respectively) were administered through the renal artery immediately after reperfusion. In vitro, THP-1 cells were stimulated with IFN-γ in the presence of conditioned medium from HIF-MSCs or untreated MSCs.

Results

Administration of HIF-MSCs attenuated renal fibrosis more effectively than untreated MSCs at 21 days post-IRI, as demonstrated by reduced expression of α-SMA, TGF-β1, and collagen type I. Furthermore, at 7 days post-IRI, HIF-MSCs suppressed renal inflammation more potently than untreated MSCs, as evidenced by reduced immune cell infiltration as well as decreased phosphorylated NF-κB levels and NLRP3 expression. In vitro, conditioned medium from HIF-MSCs significantly suppressed NF-κB activation and the expression of inflammasome-related molecules, including NLRP3, ASC, and IL-1β, in IFN-γ-stimulated THP-1 cells. Bulk RNA sequencing of the two MSC groups identified stanniocalcin-1 (STC-1) as a highly upregulated factor in HIF-MSCs. Notably, STC-1 knockdown attenuated the suppressive effects of HIF-MSCs on phosphorylated NF-κB levels and NLRP3 expression in IFN-γ-stimulated THP-1 cells.

Conclusion

These findings suggest that roxadustat-preconditioned MSCs exert potent anti-inflammatory and anti-fibrotic effects through STC-1–mediated suppression of the NF-κB/NLRP3 inflammasome axis, and may represent a promising therapeutic strategy for mitigating renal inflammation and fibrosis.

Funding

• Government Support – Non-U.S.