Abstract: SA-PO156
NINJ1 Has a Pathogenic Role in Kidney Ischemia-Reperfusion Injury
Session Information
- AKI: Metabolism and Cell Death
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Yin, Jianyong, Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
- Wang, Niansong, Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
Background
Programmed cell death (PCD) plays a pivotal role in the pathogenesis of AKI. It has been proved that various PCDS such as pyroptosis, necroptosis and ferroptsis can induce plasma membrane rupture (PMR) and release of damage associated molecular patterns (DAMPs), further activating inflammatory responses, and lead to kidney tissue damage. PMR is the common ultimate event in a variety of lytic cell death. Nerve injury-induced protein 1 (NINJ1) is a cell adhesion molecule highly expressed in immune cells and kidney. Recent studies indicate that NINJ1 is a key executive protein of PMR during various PCD. Therefore, we speculate that NINJ1 mediates PMR in tubule cells during PCD and subsequently activates inflammation, which may be the primary molecular mechanism of its pathogenic role in AKI.
Methods
We examined renal NINJ1 oligomerization in patients with AKI and AKI mice model. Male C57BL/6J were subjected to bilateral renal ischemia-reperfusion to induce AKI. Tubule cell-specific NINJ1 knockout mice was utilized to determine the pathogenic role of NINJ1 in AKI. Renal function, tubular cell death, release of HMGB1 and pro-inflammatory cytokines was assessed. Besides, we determined the role of NINJ1 in cell damage induced by hypoxia reoxygenation in primary renal tubular epithelial cells.
Results
The expression of NINJ1 was significantly increased in AKI model and kidney specimens of AKI patients. Tubular cell-specific knockout of NINJ1 remarkably ameliorated ischemia-reperfusion induced renal dysfunction and pathological injury. Moreover, tubular cell death and the levels of HMGB1, IL-1β were significantly blunted in NINJ1 knockout mice compared with WT mice. Additionally, hypoxia and reoxygenation induced NINJ1 oligomerization in renal tubular cells, while knockout of NINJ1 significantly decreased the LDH, which is the standard marker of PMR.
Conclusion
NINJ1 mediated PMR and subsequent release of DAMPs is critically involved in the pathogenesis of AKI and blockade of NINJ1 may be a novel therapeutic strategy for the treatment of AKI.
Funding
- Government Support – Non-U.S.