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Integrative transcriptomic and single-cell analyses identify CD74 as a candidate regulator of ferroptosis in renal tubular cells during nephrolithiasis.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Integrative transcriptomic and single-cell analyses identify CD74 as a candidate regulator of ferroptosis in renal tubular cells during nephrolithiasis.
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.
References: J Pathol. 2019 Apr;247(5):697-707. (PMID: 30714148)
Biochem Pharmacol. 2026 Apr;246:117720. (PMID: 41558614)
J Transl Int Med. 2024 Mar 21;12(1):22-34. (PMID: 38525436)
Adv Sci (Weinh). 2025 Mar;12(10):e2403992. (PMID: 39836526)
Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16836-41. (PMID: 25385600)
Int Immunopharmacol. 2025 Mar 06;149:114248. (PMID: 39929098)
Life Sci. 2023 May 15;321:121608. (PMID: 36958437)
J Transl Int Med. 2025 Dec 12;13(6):512-515. (PMID: 41438464)
Mol Biol Rep. 2025 Dec 10;53(1):171. (PMID: 41369886)
Cell Death Discov. 2025 Jun 17;11(1):279. (PMID: 40527896)
Kidney Int. 2024 Apr;105(4):775-790. (PMID: 38286179)
Nat Rev Nephrol. 2021 Jun;17(6):417-433. (PMID: 33514941)
Front Oncol. 2026 Jul 14;16:1835555. (PMID: 42524008)
Biomed Pharmacother. 2020 Feb;122:109772. (PMID: 31918290)
Cytokine Growth Factor Rev. 2013 Feb;24(1):23-40. (PMID: 22959722)
Cancer Biol Ther. 2024 Dec 31;25(1):2403197. (PMID: 39345091)
Adv Sci (Weinh). 2024 Dec;11(48):e2408945. (PMID: 39498889)
Cell Mol Life Sci. 2024 Jul 11;81(1):296. (PMID: 38992165)
Cytokine Growth Factor Rev. 2026 Oct;91:22-42. (PMID: 42413190)
Mol Biol Rep. 2024 Feb 20;51(1):314. (PMID: 38376557)
Nat Rev Nephrol. 2025 Nov;21(11):794-808. (PMID: 40790363)
Nat Rev Clin Oncol. 2021 May;18(5):280-296. (PMID: 33514910)
Cell Physiol Biochem. 2025 Sep 3;59(5):569-588. (PMID: 40916855)
Front Pharmacol. 2024 Sep 16;15:1437113. (PMID: 39351084)
Cell Immunol. 2015 Nov-Dec;298(1-2):25-32. (PMID: 26321123)
Inflamm Res. 2017 Mar;66(3):209-216. (PMID: 27752708)
Theranostics. 2023 May 8;13(9):2757-2773. (PMID: 37284446)
J Transl Int Med. 2025 Jan 10;12(6):581-591. (PMID: 39802445)
Redox Rep. 2026 Dec;31(1):2643967. (PMID: 41833934)
Cell Death Dis. 2023 Mar 21;14(3):205. (PMID: 36944609)
Nat Rev Dis Primers. 2016 Feb 25;2:16008. (PMID: 27188687)
Int J Biol Sci. 2023 May 11;19(9):2678-2694. (PMID: 37324941)
J Biol Chem. 2018 Dec 21;293(51):19740-19760. (PMID: 30366984)
Cell Mol Life Sci. 2017 Oct;74(19):3631-3645. (PMID: 28551825)
Cell Death Dis. 2023 Sep 22;14(9):628. (PMID: 37739961)
Cell. 2012 May 25;149(5):1060-72. (PMID: 22632970)
Nat Rev Nephrol. 2023 May;19(5):281-299. (PMID: 36959481)
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
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  Data: Integrative transcriptomic and single-cell analyses identify CD74 as a candidate regulator of ferroptosis in renal tubular cells during nephrolithiasis.
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  Data: <searchLink fieldCode="AU" term="%22Yang+J%22">Yang J</searchLink>; Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.<br /><searchLink fieldCode="AU" term="%22Wang+B%22">Wang B</searchLink>; Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.<br /><searchLink fieldCode="AU" term="%22Xun+Y%22">Xun Y</searchLink>; Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.<br /><searchLink fieldCode="AU" term="%22Yu+X%22">Yu X</searchLink>; Department of Urology, Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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  Data: <searchLink fieldCode="JN" term="%228701128%22">Renal failure</searchLink> [Ren Fail] 2026 Dec; Vol. 48 (1), pp. 2728222. <i>Date of Electronic Publication: </i>2026 Sep 21.
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– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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.
– Name: Ref
  Label: References
  Group: RefInfo
  Data: J Pathol. 2019 Apr;247(5):697-707. (PMID: <searchLink fieldCode="PM" term="%2230714148%22">30714148)</searchLink><br />Biochem Pharmacol. 2026 Apr;246:117720. (PMID: <searchLink fieldCode="PM" term="%2241558614%22">41558614)</searchLink><br />J Transl Int Med. 2024 Mar 21;12(1):22-34. (PMID: <searchLink fieldCode="PM" term="%2238525436%22">38525436)</searchLink><br />Adv Sci (Weinh). 2025 Mar;12(10):e2403992. (PMID: <searchLink fieldCode="PM" term="%2239836526%22">39836526)</searchLink><br />Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16836-41. (PMID: <searchLink fieldCode="PM" term="%2225385600%22">25385600)</searchLink><br />Int Immunopharmacol. 2025 Mar 06;149:114248. (PMID: <searchLink fieldCode="PM" term="%2239929098%22">39929098)</searchLink><br />Life Sci. 2023 May 15;321:121608. (PMID: <searchLink fieldCode="PM" term="%2236958437%22">36958437)</searchLink><br />J Transl Int Med. 2025 Dec 12;13(6):512-515. (PMID: <searchLink fieldCode="PM" term="%2241438464%22">41438464)</searchLink><br />Mol Biol Rep. 2025 Dec 10;53(1):171. (PMID: <searchLink fieldCode="PM" term="%2241369886%22">41369886)</searchLink><br />Cell Death Discov. 2025 Jun 17;11(1):279. (PMID: <searchLink fieldCode="PM" term="%2240527896%22">40527896)</searchLink><br />Kidney Int. 2024 Apr;105(4):775-790. (PMID: <searchLink fieldCode="PM" term="%2238286179%22">38286179)</searchLink><br />Nat Rev Nephrol. 2021 Jun;17(6):417-433. (PMID: <searchLink fieldCode="PM" term="%2233514941%22">33514941)</searchLink><br />Front Oncol. 2026 Jul 14;16:1835555. (PMID: <searchLink fieldCode="PM" term="%2242524008%22">42524008)</searchLink><br />Biomed Pharmacother. 2020 Feb;122:109772. (PMID: <searchLink fieldCode="PM" term="%2231918290%22">31918290)</searchLink><br />Cytokine Growth Factor Rev. 2013 Feb;24(1):23-40. (PMID: <searchLink fieldCode="PM" term="%2222959722%22">22959722)</searchLink><br />Cancer Biol Ther. 2024 Dec 31;25(1):2403197. (PMID: <searchLink fieldCode="PM" term="%2239345091%22">39345091)</searchLink><br />Adv Sci (Weinh). 2024 Dec;11(48):e2408945. (PMID: <searchLink fieldCode="PM" term="%2239498889%22">39498889)</searchLink><br />Cell Mol Life Sci. 2024 Jul 11;81(1):296. (PMID: <searchLink fieldCode="PM" term="%2238992165%22">38992165)</searchLink><br />Cytokine Growth Factor Rev. 2026 Oct;91:22-42. (PMID: <searchLink fieldCode="PM" term="%2242413190%22">42413190)</searchLink><br />Mol Biol Rep. 2024 Feb 20;51(1):314. (PMID: <searchLink fieldCode="PM" term="%2238376557%22">38376557)</searchLink><br />Nat Rev Nephrol. 2025 Nov;21(11):794-808. (PMID: <searchLink fieldCode="PM" term="%2240790363%22">40790363)</searchLink><br />Nat Rev Clin Oncol. 2021 May;18(5):280-296. (PMID: <searchLink fieldCode="PM" term="%2233514910%22">33514910)</searchLink><br />Cell Physiol Biochem. 2025 Sep 3;59(5):569-588. (PMID: <searchLink fieldCode="PM" term="%2240916855%22">40916855)</searchLink><br />Front Pharmacol. 2024 Sep 16;15:1437113. (PMID: <searchLink fieldCode="PM" term="%2239351084%22">39351084)</searchLink><br />Cell Immunol. 2015 Nov-Dec;298(1-2):25-32. (PMID: <searchLink fieldCode="PM" term="%2226321123%22">26321123)</searchLink><br />Inflamm Res. 2017 Mar;66(3):209-216. (PMID: <searchLink fieldCode="PM" term="%2227752708%22">27752708)</searchLink><br />Theranostics. 2023 May 8;13(9):2757-2773. (PMID: <searchLink fieldCode="PM" term="%2237284446%22">37284446)</searchLink><br />J Transl Int Med. 2025 Jan 10;12(6):581-591. (PMID: <searchLink fieldCode="PM" term="%2239802445%22">39802445)</searchLink><br />Redox Rep. 2026 Dec;31(1):2643967. (PMID: <searchLink fieldCode="PM" term="%2241833934%22">41833934)</searchLink><br />Cell Death Dis. 2023 Mar 21;14(3):205. (PMID: <searchLink fieldCode="PM" term="%2236944609%22">36944609)</searchLink><br />Nat Rev Dis Primers. 2016 Feb 25;2:16008. (PMID: <searchLink fieldCode="PM" term="%2227188687%22">27188687)</searchLink><br />Int J Biol Sci. 2023 May 11;19(9):2678-2694. (PMID: <searchLink fieldCode="PM" term="%2237324941%22">37324941)</searchLink><br />J Biol Chem. 2018 Dec 21;293(51):19740-19760. (PMID: <searchLink fieldCode="PM" term="%2230366984%22">30366984)</searchLink><br />Cell Mol Life Sci. 2017 Oct;74(19):3631-3645. (PMID: <searchLink fieldCode="PM" term="%2228551825%22">28551825)</searchLink><br />Cell Death Dis. 2023 Sep 22;14(9):628. (PMID: <searchLink fieldCode="PM" term="%2237739961%22">37739961)</searchLink><br />Cell. 2012 May 25;149(5):1060-72. (PMID: <searchLink fieldCode="PM" term="%2222632970%22">22632970)</searchLink><br />Nat Rev Nephrol. 2023 May;19(5):281-299. (PMID: <searchLink fieldCode="PM" term="%2236959481%22">36959481)</searchLink>
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  Data: <i>Keywords: </i>CD74; NF-κB signaling pathway; Nephrolithiasis; ferroptosis; oxidative stress
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    Subjects:
      – SubjectFull: NF-kappa B metabolism
        Type: general
      – SubjectFull: Phospholipid Hydroperoxide Glutathione Peroxidase metabolism
        Type: general
      – SubjectFull: Phospholipid Hydroperoxide Glutathione Peroxidase genetics
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      – SubjectFull: Animals
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      – SubjectFull: Mice
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      – SubjectFull: Humans
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      – SubjectFull: Oxidative Stress
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      – SubjectFull: Signal Transduction
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      – SubjectFull: Ferroptosis genetics
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      – SubjectFull: Nephrolithiasis genetics
        Type: general
      – SubjectFull: Nephrolithiasis pathology
        Type: general
      – SubjectFull: Nephrolithiasis metabolism
        Type: general
      – SubjectFull: Kidney Tubules pathology
        Type: general
      – SubjectFull: Kidney Tubules metabolism
        Type: general
      – SubjectFull: Kidney Tubules cytology
        Type: general
      – SubjectFull: Antigens, Differentiation, B-Lymphocyte genetics
        Type: general
      – SubjectFull: Antigens, Differentiation, B-Lymphocyte metabolism
        Type: general
      – SubjectFull: Histocompatibility Antigens Class II genetics
        Type: general
      – SubjectFull: Histocompatibility Antigens Class II metabolism
        Type: general
    Titles:
      – TitleFull: Integrative transcriptomic and single-cell analyses identify CD74 as a candidate regulator of ferroptosis in renal tubular cells during nephrolithiasis.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Yang J
      – PersonEntity:
          Name:
            NameFull: Wang B
      – PersonEntity:
          Name:
            NameFull: Xun Y
      – PersonEntity:
          Name:
            NameFull: Yu X
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 12
              Text: 2026 Dec
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1525-6049
          Numbering:
            – Type: volume
              Value: 48
            – Type: issue
              Value: 1
          Titles:
            – TitleFull: Renal failure
              Type: main
ResultId 1