Mesenchymal stromal cells reduce ferroptosis of podocytes by activating the Nrf2/HO-1/GPX4 pathway in lupus nephritis
- Chang Liu 1, Xuanqi Liu 2, Yujiao Wang 1, Honghong Yu 3, Qi Li 2, Yuanyuan Zheng 2, Yao Fu 4, Genhong Yao 5, Lingyun Sun 6
- Chang Liu 1, Xuanqi Liu 2, Yujiao Wang 1
- 1Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, China.
- 2Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China.
- 3Department of Rheumatology and Immunology, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, China.
- 4Department of Pathology, Affiliated Drum Tower Hospital, Medical School of Nanjing University.
- 5Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China; Department of Rheumatology and Immunology, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, China.
- 6Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, China; Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China; Department of Rheumatology and Immunology, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, China.
- 0Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, China.
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View abstract on PubMed
Summary
This summary is machine-generated.Mesenchymal stromal cells (MSCs) inhibit ferroptosis in lupus nephritis (LN) by modulating the Nrf2/HO-1/GPX4 pathway, offering a potential therapeutic strategy for kidney disease.
Area Of Science
- Nephrology
- Immunology
- Cell Biology
Background
- Ferroptosis, a regulated cell death pathway, is implicated in kidney diseases, including lupus nephritis (LN).
- Podocyte injury and renal dysfunction in LN are linked to ferroptosis.
- Mesenchymal stromal cells (MSCs) show promise for repairing podocyte injury in LN.
Purpose Of The Study
- To investigate whether MSCs regulate ferroptosis in podocytes within the context of LN.
- To elucidate the underlying molecular mechanisms of MSC-mediated podocyte protection in LN.
Main Methods
- MSCs were administered to MRL/lpr mice with LN.
- Ferroptosis biomarkers, podocyte markers (WT-1, synaptopodin), and the Nrf2/HO-1 pathway were assessed in vivo.
- In vitro studies used mouse podocyte cell line MPC-5 treated with puromycin aminonucleoside (PAN) and MSCs.
Main Results
- MSC transplantation improved LN symptoms and podocyte markers in MRL/lpr mice.
- MSC treatment upregulated ferroptosis regulators (GPX4, ACSL4) and activated the Nrf2/HO-1 pathway in podocytes.
- In vitro, MSCs protected podocytes from PAN-induced ferroptosis by stabilizing actin fibers and promoting Nrf2 nuclear translocation, effects reversed by a ferroptosis inhibitor.
Conclusions
- Ferroptosis activation is a key factor in LN pathogenesis.
- MSCs mitigate podocyte injury in LN by inhibiting ferroptosis via the Nrf2/HO-1/GPX4 pathway.
- Targeting the Nrf2/HO-1/GPX4 pathway presents a novel therapeutic avenue for LN.
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