Abstract: TH-PO1179
MIT-001 Attenuates Kidney Damage and Fibrosis Induced by Ischemia-Reperfusion Injury
Session Information
- CKD: Mechanisms, AKI, and Beyond - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Park, Kyungho, Chungnam National University Hospital, Daejeon, Korea (the Republic of)
- Choi, Dae Eun, Chungnam National University Hospital, Daejeon, Korea (the Republic of)
- Lee, Eu Jin, Chungnam National University Hospital, Daejeon, Korea (the Republic of)
- Ham, Youngrok, Chungnam National University School of Medicine, Daejeon, Korea (the Republic of)
- Park, Heewon, Chungnam National University Sejong Hospital, Sejong, Korea (the Republic of)
- Kim, Hae Ri, Chungnam National University Sejong Hospital, Sejong, Korea (the Republic of)
Background
Renal ischemia-reperfusion injury (IRI) is a major contributor to the development of renal fibrosis, a hallmark of chronic kidney disease (CKD). IRI exacerbates inflammatory responses, leading to ferroptosis and progressive fibrosis. MIT-001, a small molecule with known anti-necrotic and anti-inflammatory properties, has shown therapeutic promise in various models of organ injury. This study aimed to evaluate the antifibrotic, anti-inflammatory, and anti-ferroptotic effects of MIT-001 in a murine model of IRI-induced renal fibrosis and to explore its underlying mechanisms.
Methods
Eight-week-old male C57BL/6 mice were subjected to bilateral renal ischemia-reperfusion injury and treated with MIT-001. Kidney and serum samples were collected on days 1, 3, and 7 post-injury. In vitro assays were performed using TGF-β-treated HK-2 human proximal tubule cells to assess fibrosis-related pathways.
Results
MIT-001 treatment significantly improved renal function, as indicated by decreased serum creatinine and blood urea nitrogen levels at 3 and 7 days post-IRI. Histological and molecular analyses demonstrated that MIT-001 markedly reduced fibrotic markers including F4/80, collagen IV, α-smooth muscle actin (α-SMA), and TGF-β, while enhancing the expression of the epithelial marker E-cadherin. MIT-001 also suppressed ferroptosis, evidenced by upregulation of xCT, SLC7A11, and GPX4, and downregulation of 4-HNE. Furthermore, MIT-001 significantly inhibited inflammatory responses, as shown by reduced levels of HMGB1 and nuclear NF-κB in renal tissues.
Conclusion
MIT-001 effectively mitigates renal fibrosis following ischemia-reperfusion injury by suppressing inflammation, oxidative stress, and ferroptosis. These findings highlight MIT-001 as a promising therapeutic candidate for preventing CKD progression after acute kidney injury.