The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Ferroptosis, but Not Necroptosis, Is Important in Nephrotoxic Folic Acid–Induced AKI
Open accessAbstract
AKI is histologically characterized by necrotic cell death and inflammation. Diverse pathways of regulated necrosis have been reported to contribute to AKI, but the molecular regulators involved remain unclear. We explored the relative contributions of ferroptosis and necroptosis to folic acid (FA)–induced AKI in mice. FA-AKI in mice associates with lipid peroxidation and downregulation of glutathione metabolism proteins, features that are typical of ferroptotic cell death. We show that ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, preserved renal function and decreased histologic injury, oxidative stress, and tubular cell death in this model. With respect to the immunogenicity of ferroptosis, Fer-1 prevented the upregulation of IL-33, an alarmin linked to necroptosis, and other chemokines and cytokines and prevented macrophage infiltration and Klotho downregulation. In contrast, the pancaspase inhibitor zVAD-fmk did not protect against FA-AKI. Additionally, although FA-AKI resulted in increased protein expression of the necroptosis mediators receptor–interacting protein kinase 3 (RIPK3) and mixed lineage domain–like protein (MLKL), targeting necroptosis with the RIPK1 inhibitor necrostatin-1 or genetic deficiency of RIPK3 or MLKL did not preserve renal function. Indeed, compared with wild-type mice, MLKL knockout mice displayed more severe AKI. However, RIPK3 knockout mice with AKI had less inflammation than their wild-type counterparts, and this effect associated with higher IL-10 concentration and regulatory T cell-to-leukocyte ratio in RIPK3 knockout mice. These data suggest that ferroptosis is the primary cause of FA-AKI and that immunogenicity secondary to ferroptosis may further worsen the damage, although necroptosis-related proteins may have additional roles in AKI.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“A similar protective effect is observed in GPX4-independent models of renal ischemic or toxic injury [540, 592], Parkinson disease [593], and other human pathologies [594].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [592]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Dixon, S. J., Lemberg, K. M., Lamprecht, M. R., Skouta, R., Zaitsev, E. M., Gleason, C. E., Patel, D. N., Bauer, A. J., Cantley, A. M., Yang, W. S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.042 · Cited by 18,691
Regulation of Ferroptotic Cancer Cell Death by GPX4
Yang, W. S., SriRamaratnam, R., Welsch, M. E., Shimada, K., Skouta, R., Viswanathan, V. S., Cheah, J. H., Clemons, P. A., Shamji, A. F., Clish, C. B., et al. (2014) · Cell · doi:10.1016/j.cell.2013.12.010 · Cited by 7,713
Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice
Friedmann Angeli, J. P., Schneider, M., Proneth, B., Tyurina, Y. Y., Tyurin, V. A., Hammond, V. J., Herbach, N., Aichler, M., Walch, A., Eggenhofer, E., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3064 · Cited by 3,732
Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 Kinase
Sun, L., Wang, H., Wang, Z., He, S., Chen, S., Liao, D., Wang, L., Yan, J., Liu, W., Lei, X., et al. (2012) · Cell · doi:10.1016/j.cell.2011.11.031 · Cited by 2,698
Bellomo, R., Kellum, J. A., & Ronco, C. (2012) · The Lancet · doi:10.1016/s0140-6736(11)61454-2 · Cited by 2,607
Cho, Y., Challa, S., Moquin, D., Genga, R., Ray, T. D., Guildford, M., & Chan, F. K.-M. (2009) · Cell · doi:10.1016/j.cell.2009.05.037 · Cited by 2,435
Necroptosis: The Release of Damage-Associated Molecular Patterns and Its Physiological Relevance
Kaczmarek, A., Vandenabeele, P., & Krysko, D. V. (2013) · Immunity · doi:10.1016/j.immuni.2013.02.003 · Cited by 1,411
Ferrostatins Inhibit Oxidative Lipid Damage and Cell Death in Diverse Disease Models
Skouta, R., Dixon, S. J., Wang, J., Dunn, D. E., Orman, M., Shimada, K., Rosenberg, P. A., Lo, D. C., Weinberg, J. M., Linkermann, A., et al. (2014) · Journal of the American Chemical Society · doi:10.1021/ja411006a · Cited by 1,146
Self-citationSynchronized renal tubular cell death involves ferroptosis
Linkermann, A., Skouta, R., Himmerkus, N., Mulay, S. R., Dewitz, C., De Zen, F., Prokai, A., Zuchtriegel, G., Krombach, F., Welz, P.-S., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1415518111 · Cited by 1,126
Self-citationLinkermann, A., & Green, D. R. (2014) · New England Journal of Medicine · doi:10.1056/nejmra1310050 · Cited by 1,103
Self-citation
Cited by
Sorted by citations
Ferroptosis: mechanisms, biology and role in disease
Jiang, X., Stockwell, B. R., & Conrad, M. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00324-8 · Cited by 7,973
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
Self-citationFerroptosis: past, present and future
Li, J., Cao, F., Yin, H.-L., Huang, Z.-J., Lin, Z.-T., Mao, N., Sun, B., & Wang, G. (2020) · Cell Death & Disease · doi:10.1038/s41419-020-2298-2 · Cited by 4,171
Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis
Su, L.-J., Zhang, J.-H., Gomez, H., Murugan, R., Hong, X., Xu, D., Jiang, F., & Peng, Z.-Y. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/5080843 · Cited by 2,166
Targeting the progression of chronic kidney disease
Ruiz-Ortega, M., Rayego-Mateos, S., Lamas, S., Ortiz, A., & Rodrigues-Diez, R. R. (2020) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0248-y · Cited by 979
Self-citation
Metadata
- Authors
- Martin-Sanchez, D., Ruiz-Andres, O., Poveda, J., Carrasco, S., Cannata-Ortiz, P., Sanchez-Niño, M. D., Ruiz Ortega, M., Egido, J., Linkermann, A., Ortiz, A., & Sanz, A. B.
- Affiliations
- Division of Nephrology and
- Department of Pathology, Instituto de Investigacion Sanitaria (IIS)-Fundacion Jimenez Diaz and
- Christian-Albrechts-Universität zu Kiel (DE)
- Corresponding author
- Poveda, Jonay
- Carrasco, Susana
- Linkermann, Andreas
- Sanz, Ana B.
- Venue
- Journal of the American Society of Nephrology
- Published
- 2016-06-27
- Volume
- 28
- Issue
- 1
- Pages
- 218-229
- ISSN
- 1046-6673 (ISSN-L)
- 1533-3450
- PMC
- PMC5198282
- OpenAlex
- W2470889344
- Cited by
- 564
- References
- 37
- Citations by year
- 2026: 44 · 2025: 72 · 2024: 84 · 2023: 79 · 2022: 99 · 2021: 65 · 2020: 46 · 2019: 31 · 2018: 31 · 2017: 13
- FWCI
- 24.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American Society of Nephrology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- ferroptosis, necroptosis, acute kidney injury, folic acid nephrotoxicity, ferrostatin-1, regulated necrosis, lipid peroxidation, glutathione metabolism, IL-33, RIPK3, MLKL, necrostatin-1, Klotho, macrophage infiltration, renal inflammation, oxidative stress, regulatory T cells
- MeSH terms
- Animals, Folic Acid, Iron, Mice, Inbred C57BL, Necrosis, Cell Death, Mice, Acute Kidney Injury
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
