Academic Journal
Integrative transcriptomic and single-cell analyses identify CD74 as a candidate regulator of ferroptosis in renal tubular cells during nephrolithiasis.
| Τίτλος: | Integrative transcriptomic and single-cell analyses identify CD74 as a candidate regulator of ferroptosis in renal tubular cells during nephrolithiasis. |
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| Συγγραφείς: | Yang J; Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Wang B; Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Xun Y; Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Yu X; Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. |
| Πηγή: | Renal failure [Ren Fail] 2026 Dec; Vol. 48 (1), pp. 2728222. Date of Electronic Publication: 2026 Sep 21. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Informa Healthcare Country of Publication: England NLM ID: 8701128 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-6049 (Electronic) Linking ISSN: 0886022X NLM ISO Abbreviation: Ren Fail Subsets: MEDLINE |
| Imprint Name(s): | Publication: London : Informa Healthcare Original Publication: New York, N.Y. : M. Dekker, c1987- |
| Ιατρικοί όροι (MeSH): | Ferroptosis*/genetics , Nephrolithiasis*/genetics , Nephrolithiasis*/pathology , Nephrolithiasis*/metabolism , Kidney Tubules*/pathology , Kidney Tubules*/metabolism , Kidney Tubules*/cytology , Antigens, Differentiation, B-Lymphocyte*/genetics , Antigens, Differentiation, B-Lymphocyte*/metabolism , Histocompatibility Antigens Class II*/genetics , Histocompatibility Antigens Class II*/metabolism, NF-kappa B/metabolism ; Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics ; Coenzyme A Ligases/metabolism ; Coenzyme A Ligases/genetics ; Epithelial Cells/metabolism ; Animals ; Mice ; Humans ; Oxidative Stress ; Signal Transduction ; Cell Line ; Disease Models, Animal ; Single-Cell Gene Expression Analysis ; Male ; Transcriptome |
| Περίληψη: | Nephrolithiasis incidence has risen with frequent recurrence, and injury to renal tubular epithelial cells is central to its pathology. Ferroptosis, an iron-dependent form of regulated cell death, has been implicated in kidney diseases, but its role in nephrolithiasis remains unclear. In this study, we investigated whether CD74 is associated with ferroptosis-related tubular injury during nephrolithiasis and explored the potential involvement of NF-κB signaling. A glyoxylate-induced mouse model showed prominent calcium oxalate deposition, impaired renal function, altered expression of ACSL4 and GPX4, and increased oxidative stress. Integrating bulk transcriptomics, protein-protein interaction networks, bioinformatics, and a public single-cell RNA-sequencing dataset, we identified CD74 as a candidate ferroptosis-associated gene showing increased expression during nephrolithiasis progression. In vitro, oxalate exposure in human HK-2 cells induced CD74 upregulation together with ferroptosis-associated molecular and biochemical changes. CD74 knockdown improved cell viability and redox homeostasis and attenuated ferroptosis-associated marker changes, whereas CD74 overexpression aggravated oxidative injury and ferroptosis. Mechanistically, CD74 modulation was associated with changes in NF-κB signaling activity, and pharmacological modulation of NF-κB partially reversed the corresponding cellular phenotypes. Together, these findings support a potential role of CD74-associated NF-κB signaling in ferroptosis-related tubular injury during nephrolithiasis. These findings suggest that the CD74/NF-κB axis may represent a potential therapeutic direction and provide mechanistic insight for future studies. |
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| Contributed Indexing: | Keywords: CD74; NF-κB signaling pathway; Nephrolithiasis; ferroptosis; oxidative stress |
| Substance Nomenclature: | 0 (invariant chain) 0 (Antigens, Differentiation, B-Lymphocyte) 0 (Histocompatibility Antigens Class II) 0 (NF-kappa B) EC 1.11.1.12 (Phospholipid Hydroperoxide Glutathione Peroxidase) EC 1.11.1.9 (glutathione peroxidase 4, mouse) EC 6.2.1.- (Coenzyme A Ligases) |
| Entry Date(s): | Date Created: 20260922 Date Completed: 20260922 Latest Revision: 20260925 |
| Update Code: | 20260925 |
| PubMed Central ID: | PMC13600292 |
| DOI: | 10.1080/0886022X.2026.2728222 |
| PMID: | 42768906 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1525-6049 |
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| DOI: | 10.1080/0886022X.2026.2728222 |