SpringerLink
Log in

Ferroptosis in pancreatic diseases: potential opportunities and challenges that require attention

  • Review Article
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

The pancreas is an abdominal organ with both endocrine and exocrine functions, and patients with pancreatic diseases suffer tremendously. The regulated cell death of various cells in the pancreas is thought to play a key role in disease development. As one of the newly discovered regulated cell death modalities, ferroptosis has the potential for therapeutic applications in the study of multiple diseases. Ferroptosis has been observed in several pancreatic diseases, but its role in pancreatic diseases has not been systematically elucidated or reviewed. Understanding the occurrence of ferroptosis in various pancreatic diseases after damage to the different cell types is crucial in determining disease progression, evaluating targeted therapies, and predicting disease prognosis. Herein, we summarize the research progress associated with ferroptosis in four common pancreatic diseases, namely acute pancreatitis, chronic pancreatitis, pancreatic ductal adenocarcinoma, and diabetes mellitus. Furthermore, the elucidation of ferroptosis in rare pancreatic diseases may provide sociological benefits in the future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Availability of data and materials

Not applicable.

Abbreviations

AP:

Acute pancreatitis

CP:

Chronic pancreatitis

PDAC:

Pancreatic ductal adenocarcinoma

RCD:

Regulated cell death

ROS:

Reactive oxygen species

PUFA:

Polyunsaturated fatty acid

LOXs:

Lipoxygenases

L-OOH:

Lipid hydroperoxide

ACSL4:

Ester acyl-CoA synthetase long-chain family member 4

LPCAT3:

Lysophosphatidylcholine acyltransferase 3

PE:

Phosphatidylethanolamine

PEBP1:

PE-binding protein 1

xC–:

The cysteine/glutamate antiporter

GPX4:

Glutathione peroxidase-4

TFR:

Transferrin receptor

PSC:

Pancreatic stellate cells

T1DM:

Type 1 diabetes mellitus

TGF-β1:

Transforming growth factor-β1

References

  1. Chen Q, Wang WJ, Jia YX, et al. Effect of the transcription factor YY1 on the development of pancreatic endocrine and exocrine tumors: a narrative review. Cell Biosci. 2021;11:86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Tang ZC, Chu Y, Tan YY, Li J, Gao S. Pancreatic and duodenal homeobox-1 in pancreatic ductal adenocarcinoma and diabetes mellitus. Chin Med J. 2020;133:344–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Poudel A, Fowler JL, Zielinski MC, Kilimnik G, Hara M. Stereological analyses of the whole human pancreas. Sci Rep. 2016;6:34049.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Li Y, Tang CG, Zhao Y, Cao WY, Qu GF. Outcomes and prognostic factors of patients with stage IB and IIA pancreatic cancer according to the 8(th) edition American Joint Committee on Cancer criteria. World J Gastroenterol. 2017;23:2757–62.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Han L, Zhao Z, Yang K, et al. Application of exosomes in the diagnosis and treatment of pancreatic diseases. Stem Cell Res Ther. 2022;13:153.

    Article  PubMed  PubMed Central  Google Scholar 

  6. **ao AY, Tan ML, Wu LM, et al. Global incidence and mortality of pancreatic diseases: a systematic review, meta-analysis, and meta-regression of population-based cohort studies. Lancet Gastroenterol Hepatol. 2016;1:45–55.

    Article  PubMed  Google Scholar 

  7. Grant TJ, Hua K, Singh A. Molecular pathogenesis of pancreatic cancer. Prog Mol Biol Transl Sci. 2016;144:241–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Boxhoorn L, Voermans RP, Bouwense SA, et al. Acute pancreatitis. Lancet (London, England). 2020;396:726–34.

    Article  PubMed  Google Scholar 

  9. Lew D, Afghani E, Pandol S. Chronic pancreatitis: current status and challenges for prevention and treatment. Dig Dis Sci. 2017;62:1702–12.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Cannon A, Thompson CM, Bhatia R, et al. Molecular mechanisms of pancreatic myofibroblast activation in chronic pancreatitis and pancreatic ductal adenocarcinoma. J Gastroenterol. 2021;56:689–703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Álvarez-Almazán S, Filisola-Villaseñor JG, Alemán-González-Duhart D, Tamay-Cach F, Mendieta-Wejebe JE. Current molecular aspects in the development and treatment of diabetes. J Physiol Biochem. 2020;76:13–35.

    Article  PubMed  Google Scholar 

  12. Petrov MS, Yadav D. Global epidemiology and holistic prevention of pancreatitis. Nat Rev Gastroenterol Hepatol. 2019;16:175–84.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Yadav D, Lowenfels AB. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology. 2013;144:1252–61.

    Article  PubMed  Google Scholar 

  14. Gliem N, Ammer-Herrmenau C, Ellenrieder V, Neesse A. Management of severe acute pancreatitis: an update. Digestion. 2021;102:503–7.

    Article  PubMed  Google Scholar 

  15. Yi J, Wu S, Tan S, et al. Berberine alleviates liver fibrosis through inducing ferrous redox to activate ROS-mediated hepatic stellate cells ferroptosis. Cell Death Discov. 2021;7:374.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Naji A, Suganuma N, Espagnolle N, et al. Rationale for determining the functional potency of mesenchymal stem cells in preventing regulated cell death for therapeutic use. Stem Cells Transl Med. 2017;6:713–9.

    Article  CAS  PubMed  Google Scholar 

  17. Tan JH, Cao RC, Zhou L, et al. EMC6 regulates acinar apoptosis via APAF1 in acute and chronic pancreatitis. Cell Death Dis. 2020;11:966.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gao L, Dong X, Gong W, et al. Acinar cell NLRP3 inflammasome and gasdermin D (GSDMD) activation mediates pyroptosis and systemic inflammation in acute pancreatitis. Br J Pharmacol. 2021;178:3533–52.

    Article  CAS  PubMed  Google Scholar 

  19. Wu J, Zhang J, Zhao J, Chen S, Zhou T, Xu J. Treatment of severe acute pancreatitis and related lung injury by targeting gasdermin D-mediated pyroptosis. Front Cell Dev Biol. 2021;9: 780142.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Zheng M, Li H, Sun L, Brigstock DR, Gao R. Interleukin-6 participates in human pancreatic stellate cell activation and collagen I production via TGF-β1/Smad pathway. Cytokine. 2021;143: 155536.

    Article  CAS  PubMed  Google Scholar 

  21. Chen X, Zeh HJ, Kang R, Kroemer G, Tang D. Cell death in pancreatic cancer: from pathogenesis to therapy. Nat Rev Gastroenterol Hepatol. 2021;18:804–23.

    Article  PubMed  Google Scholar 

  22. Qian Y, Gong Y, Fan Z, et al. Molecular alterations and targeted therapy in pancreatic ductal adenocarcinoma. J Hematol Oncol. 2020;13:130.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Rojas J, Bermudez V, Palmar J, et al. Pancreatic beta cell death: novel potential mechanisms in diabetes therapy. J Diabetes Res. 2018;2018:9601801.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Demirtas L, Guclu A, Erdur FM, et al. Apoptosis, autophagy & endoplasmic reticulum stress in diabetes mellitus. Indian J Med Res. 2016;144:515–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Tang D, Kang R, Berghe TV, Vandenabeele P, Kroemer G. The molecular machinery of regulated cell death. Cell Res. 2019;29:347–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Santagostino SF, Assenmacher CA, Tarrant JC, Adedeji AO, Radaelli E. Mechanisms of regulated cell death: current perspectives. Vet Pathol. 2021;58:596–623.

    Article  CAS  PubMed  Google Scholar 

  27. Tang D, Chen X, Kang R, Kroemer G. Ferroptosis: molecular mechanisms and health implications. Cell Res. 2021;31:107–25.

    Article  CAS  PubMed  Google Scholar 

  28. Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149:1060–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. **e Y, Hou W, Song X, et al. Ferroptosis: process and function. Cell Death Differ. 2016;23:369–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Stockwell BR, Friedmann Angeli JP, Bayir H, et al. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell. 2017;171:273–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kuang F, Liu J, Tang D, Kang R. Oxidative damage and antioxidant defense in ferroptosis. Front Cell Dev Biol. 2020;8: 586578.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Chen X, Kang R, Kroemer G, Tang D. Ferroptosis in infection, inflammation, and immunity. J Exp Med. 2021;218:270–4.

    Article  Google Scholar 

  33. Wang W, Green M, Choi JE, et al. CD8(+) T cells regulate tumour ferroptosis during cancer immunotherapy. Nature. 2019;569:270–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Li D, Jiang C, Mei G, et al. Quercetin alleviates ferroptosis of pancreatic β cells in type 2 diabetes. Nutrients. 2020;12:2954.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Yang WS, Kim KJ, Gaschler MM, Patel M, Shchepinov MS, Stockwell BR. Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis. Proc Natl Acad Sci USA. 2016;113:E4966–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Sun S, Gao T, Pang B, et al. RNA binding protein NKAP protects glioblastoma cells from ferroptosis by promoting SLC7A11 mRNA splicing in an m(6)A-dependent manner. Cell Death Dis. 2022;13:73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Čepelak I, Dodig S, Dodig D. Ferroptosis: regulated cell death. Arh Hig Rada Toksikol. 2020;71:99–109.

    PubMed  PubMed Central  Google Scholar 

  38. Ma TL, Zhou Y, Wang C, et al. Targeting ferroptosis for lung diseases: exploring novel strategies in ferroptosis-associated mechanisms. Oxid Med Cell Longev. 2021;2021:1098970.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Zhao Y, Huang Z, Peng H. Molecular mechanisms of ferroptosis and its roles in hematologic malignancies. Front Oncol. 2021;11: 743006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Wenzel SE, Tyurina YY, Zhao J, et al. PEBP1 wardens ferroptosis by enabling lipoxygenase generation of lipid death signals. Cell. 2017;171:628-41.e26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kabiraj P, Valenzuela CA, Marin JE, et al. The neuroprotective role of ferrostatin-1 under rotenone-induced oxidative stress in dopaminergic neuroblastoma cells. Protein J. 2015;34:349–58.

    Article  CAS  PubMed  Google Scholar 

  42. Bogdan AR, Miyazawa M, Hashimoto K, Tsuji Y. Regulators of iron homeostasis: new players in metabolism, cell death, and disease. Trends Biochem Sci. 2016;41:274–86.

    Article  CAS  PubMed  Google Scholar 

  43. **a X, Fan X, Zhao M, Zhu P. The relationship between ferroptosis and tumors: a novel landscape for therapeutic approach. Curr Gene Ther. 2019;19:117–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Xu Y, Sang W, Zhong Y, et al. CoCrMo-nanoparticles induced peri-implant osteolysis by promoting osteoblast ferroptosis via regulating Nrf2-ARE signalling pathway. Cell Prolif. 2021;54: e13142.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Yang WS, SriRamaratnam R, Welsch ME, et al. Regulation of ferroptotic cancer cell death by GPX4. Cell. 2014;156:317–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Dolma S, Lessnick SL, Hahn WC, Stockwell BR. Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell. 2003;3:285–96.

    Article  CAS  PubMed  Google Scholar 

  47. Poursaitidis I, Wang X, Crighton T, et al. Oncogene-selective sensitivity to synchronous cell death following modulation of the amino acid nutrient cystine. Cell Rep. 2017;18:2547–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Woo JH, Shimoni Y, Yang WS, et al. Elucidating compound mechanism of action by network perturbation analysis. Cell. 2015;162:441–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Müller F, Lim JKM, Bebber CM, et al. Elevated FSP1 protects KRAS-mutated cells from ferroptosis during tumor initiation. Cell Death Differ. 2023;30(2):442–56.

    Article  PubMed  Google Scholar 

  50. Koppula P, Lei G, Zhang Y, et al. A targetable CoQ-FSP1 axis drives ferroptosis- and radiation-resistance in KEAP1 inactive lung cancers. Nat Commun. 2022;13:2206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Kazan HH, Urfali-Mamatoglu C, Gunduz U. Iron metabolism and drug resistance in cancer. Biomet Int J Role Met Ions Biol Biochem Med. 2017;30:629–41.

    CAS  Google Scholar 

  52. Qin X, Zhang J, Wang B, et al. Ferritinophagy is involved in the zinc oxide nanoparticles-induced ferroptosis of vascular endothelial cells. Autophagy. 2021;17:4266–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Mou Y, Wu J, Zhang Y, Abdihamid O, Duan C, Li B. Low expression of ferritinophagy-related NCOA4 gene in relation to unfavorable outcome and defective immune cells infiltration in clear cell renal carcinoma. BMC Cancer. 2021;21:18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lee YS, Lee DH, Jeong SY, et al. Ferroptosis-inducing agents enhance TRAIL-induced apoptosis through upregulation of death receptor 5. J Cell Biochem. 2019;120:928–39.

    Article  CAS  PubMed  Google Scholar 

  55. Lipper CH, Paddock ML, Onuchic JN, Mittler R, Nechushtai R, Jennings PA. Cancer-related neet proteins transfer 2Fe-2S clusters to anamorsin, a protein required for cytosolic iron-sulfur cluster biogenesis. PLoS One. 2015;10: e0139699.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Song J, Liu T, Yin Y, et al. The deubiquitinase OTUD1 enhances iron transport and potentiates host antitumor immunity. EMBO Rep. 2021;22: e51162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Kumfu S, Chattipakorn SC, Fucharoen S, Chattipakorn N. Effects of iron overload condition on liver toxicity and hepcidin/ferroportin expression in thalassemic mice. Life Sci. 2016;150:15–23.

    Article  CAS  PubMed  Google Scholar 

  58. Ou Y, Wang SJ, Li D, Chu B, Gu W. Activation of SAT1 engages polyamine metabolism with p53-mediated ferroptotic responses. Proc Natl Acad Sci USA. 2016;113:E6806–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Hou W, **e Y, Song X, et al. Autophagy promotes ferroptosis by degradation of ferritin. Autophagy. 2016;12:1425–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Gao M, Monian P, Quadri N, Ramasamy R, Jiang X. Glutaminolysis and transferrin regulate ferroptosis. Mol Cell. 2015;59:298–308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Liu J, Zhang C, Wang J, Hu W, Feng Z. The regulation of ferroptosis by tumor suppressor p53 and its pathway. Int J Mol Sci. 2020;21:8387.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Zhang Y, Cheng B, Wu ZW, et al. Serum soluble suppression of tumorigenicity 2 as a novel inflammatory marker predicts the severity of acute pancreatitis. World J Gastroenterol. 2021;27:6489–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Fan R, Sui J, Dong X, **g B, Gao Z. Wedelolactone alleviates acute pancreatitis and associated lung injury via GPX4 mediated suppression of pyroptosis and ferroptosis. Free Radic Biol Med. 2021;173:29–40.

    Article  CAS  PubMed  Google Scholar 

  64. Liu K, Liu J, Zou B, et al. Trypsin-mediated sensitization to ferroptosis increases the severity of pancreatitis in mice. Cell Mol Gastroenterol Hepatol. 2022;13:483–500.

    Article  PubMed  Google Scholar 

  65. Liu J, Zhu S, Zeng L, et al. DCN released from ferroptotic cells ignites AGER-dependent immune responses. Autophagy. 2021;18:1–14.

    Google Scholar 

  66. Qu B, Chu Y, Zhu F, et al. Granulocyte colony-stimulating factor enhances the therapeutic efficacy of bone marrow mesenchymal stem cell transplantation in rats with experimental acute pancreatitis. Oncotarget. 2017;8:21305–14.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Wu Q, Wang F, Hou Y, et al. The effect of allogenetic bone marrow-derived mesenchymal stem cell transplantation on lung aquaporin-1 and -5 in a rat model of severe acute pancreatitis. Hepatogastroenterology. 2012;59:965–76.

    CAS  PubMed  Google Scholar 

  68. Lanfredini S, Thapa A, O’Neill E. RAS in pancreatic cancer. Biochem Soc Trans. 2019;47:961–72.

    Article  CAS  PubMed  Google Scholar 

  69. Kapszewicz M, Małecka-Wojciesko E. Simple serum pancreatic ductal adenocarcinoma (PDAC) protein biomarkers-is there anything in sight? J Clin Med. 2021;10:5463.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Chandana S, Babiker HM, Mahadevan D. Therapeutic trends in pancreatic ductal adenocarcinoma (PDAC). Expert Opin Investig Drugs. 2019;28:161–77.

    Article  CAS  PubMed  Google Scholar 

  71. Martens S, Lefesvre P, Nicolle R, et al. Different shades of pancreatic ductal adenocarcinoma, different paths towards precision therapeutic applications. Anna Oncol Off J Eur Soc Med Oncol. 2019;30:1428–36.

    Article  CAS  Google Scholar 

  72. DeNicola GM, Karreth FA, Humpton TJ, et al. Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature. 2011;475:106–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Hingorani SR, Wang L, Multani AS, et al. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell. 2005;7:469–83.

    Article  CAS  PubMed  Google Scholar 

  74. Badgley MA, Kremer DM, Maurer HC, et al. Cysteine depletion induces pancreatic tumor ferroptosis in mice. Science (New York, NY). 2020;368:85–9.

    Article  CAS  Google Scholar 

  75. Du J, Wang X, Li Y, et al. DHA exhibits synergistic therapeutic efficacy with cisplatin to induce ferroptosis in pancreatic ductal adenocarcinoma via modulation of iron metabolism. Cell Death Dis. 2021;12:705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Kuang F, Liu J, **e Y, Tang D, Kang R. MGST1 is a redox-sensitive repressor of ferroptosis in pancreatic cancer cells. Cell Chem Biol. 2021;28:765-75.e5.

    Article  CAS  PubMed  Google Scholar 

  77. Tang R, Wu Z, Rong Z, et al. Ferroptosis-related lncRNA pairs to predict the clinical outcome and molecular characteristics of pancreatic ductal adenocarcinoma. Brief Bioinform. 2022. https://doi.org/10.1093/bib/bbab388.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Chen D, Gao W, Zang L, et al. Ferroptosis-related IncRNAs are prognostic biomarker of overall survival in pancreatic cancer patients. Front Cell Dev Biol. 2022;10: 819724.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Li J, Zhang J, Tao S, Hong J, Zhang Y, Chen W. Prognostication of pancreatic cancer using the cancer genome atlas based ferroptosis-related long non-coding RNAs. Front Genet. 2022;13: 838021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. ** H, Jia X, Ke H. A novel ferroptosis-related lncrnas signature predicts clinical prognosis and is associated with immune landscape in pancreatic cancer. Front Genet. 2022;13: 786689.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Singh VK, Yadav D, Garg PK. Diagnosis and management of chronic pancreatitis: a review. JAMA. 2019;322:2422–34.

    Article  CAS  PubMed  Google Scholar 

  82. Lowenfels AB, Maisonneuve P, Cavallini G, et al. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J Med. 1993;328:1433–7.

    Article  CAS  PubMed  Google Scholar 

  83. Bhatia R, Thompson C, Ganguly K, Singh S, Batra SK, Kumar S. Alcohol and smoking mediated modulations in adaptive immunity in pancreatitis. Cells. 2020;9:1880.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Kong L, Xu X, Zhang H, et al. Human umbilical cord-derived mesenchymal stem cells improve chronic pancreatitis in rats via the AKT-mTOR-S6K1 signaling pathway. Bioengineered. 2021;12:1986–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Zha M, Li F, Xu W, Chen B, Sun Z. Isolation and characterization of islet stellate cells in rat. Islets. 2014;6: e28701.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Zha M, Xu W, Jones PM, Sun Z. Isolation and characterization of human islet stellate cells. Exp Cell Res. 2016;341:61–6.

    Article  CAS  PubMed  Google Scholar 

  87. Watari N, Hotta Y, Mabuchi Y. Morphological studies on a vitamin A-storing cell and its complex with macrophage observed in mouse pancreatic tissues following excess vitamin A administration. Okajimas Folia Anat Jpn. 1982;58:837–58.

    Article  CAS  PubMed  Google Scholar 

  88. Moir JA, Mann J, White SA. The role of pancreatic stellate cells in pancreatic cancer. Surg Oncol. 2015;24:232–8.

    Article  PubMed  Google Scholar 

  89. Sousa CM, Biancur DE, Wang X, et al. Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. Nature. 2016;536:479–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Parker SJ, Amendola CR, Hollinshead KER, et al. Selective alanine transporter utilization creates a targetable metabolic niche in pancreatic cancer. Cancer Discov. 2020;10:1018–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Moon SM, Joo MJ, Lee YS, Kim MG. Effects of coffee consumption on insulin resistance and sensitivity: a meta-analysis. Nutrients. 2021;13:3976.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018;14:88–98.

    Article  PubMed  Google Scholar 

  93. Kanter JE, Bornfeldt KE. Impact of diabetes mellitus. Arterioscler Thromb Vasc Biol. 2016;36:1049–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Du H, Ren X, Bai J, Yang W, Gao Y, Yan S. Research progress of ferroptosis in adiposity-based chronic disease (ABCD). Oxid Med Cell Longev. 2022;2022:1052699.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Sarparanta J, García-Macia M, Singh R. Autophagy and mitochondria in obesity and type 2 diabetes. Curr Diabetes Rev. 2017;13:352–69.

    Article  CAS  PubMed  Google Scholar 

  96. Lenzen S. Chemistry and biology of reactive species with special reference to the antioxidative defence status in pancreatic β-cells. Biochim Biophys Acta. 2017;1861:1929–42.

    Article  CAS  Google Scholar 

  97. Padgett LE, Broniowska KA, Hansen PA, Corbett JA, Tse HM. The role of reactive oxygen species and proinflammatory cytokines in type 1 diabetes pathogenesis. Ann N Y Acad Sci. 2013;1281:16–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Krümmel B, Plötz T, Jörns A, Lenzen S, Mehmeti I. The central role of glutathione peroxidase 4 in the regulation of ferroptosis and its implications for pro-inflammatory cytokine-mediated beta-cell death. Biochim Biophys Acta. 2021;1867: 166114.

    Article  Google Scholar 

  99. Hamad M, Mohammed AK, Hachim MY, et al. Heme Oxygenase-1 (HMOX-1) and inhibitor of differentiation proteins (ID1, ID3) are key response mechanisms against iron-overload in pancreatic β-cells. Mol Cell Endocrinol. 2021;538: 111462.

    Article  CAS  PubMed  Google Scholar 

  100. Gautam S, Alam F, Moin S, Noor N, Arif SH. Role of ferritin and oxidative stress index in gestational diabetes mellitus. J Diabetes Metab Disord. 2021;20:1615–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Bai Y, Wang J, He Z, Yang M, Li L, Jiang H. Mesenchymal stem cells reverse diabetic nephropathy disease via lipoxin a4 by targeting transforming growth factor β (TGF-β)/smad pathway and pro-inflammatory cytokines. Med Sci Monit Int Med J Exp Clin Res. 2019;25:3069–76.

    CAS  Google Scholar 

  102. Kim S, Kang SW, Joo J, et al. Characterization of ferroptosis in kidney tubular cell death under diabetic conditions. Cell Death Dis. 2021;12:160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Zhang J, Qiu Q, Wang H, Chen C, Luo D. TRIM46 contributes to high glucose-induced ferroptosis and cell growth inhibition in human retinal capillary endothelial cells by facilitating GPX4 ubiquitination. Exp Cell Res. 2021;407: 112800.

    Article  CAS  PubMed  Google Scholar 

  104. Zheng YD, Zhang Y, Ma JY, Sang CY, Yang JL. A Carabrane-type sesquiterpenolide carabrone from carpesium cernuum inhibits SW1990 pancreatic cancer cells by inducing ferroptosis. Molecules (Basel, Switzerland). 2022;27:5841.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Ma X, Dong X, Xu Y, et al. Identification of AP-1 as a critical regulator of glutathione peroxidase 4 (GPX4) transcriptional suppression and acinar cell ferroptosis in acute pancreatitis. Antioxidants (Basel, Switzerland). 2022;12:100.

    PubMed  PubMed Central  Google Scholar 

  106. Wang Z, Dai Z, Zheng L, et al. Ferroptosis activation scoring model assists in chemotherapeutic agents’ selection and mediates cross-talk with immunocytes in malignant glioblastoma. Front Immunol. 2021;12: 747408.

    Article  CAS  PubMed  Google Scholar 

  107. Dai R, Chen G, Huang Z, et al. Establishment and characteristics of an animal model for isolated pancreatic trauma. J Trauma Acute Care Surg. 2012;73:648–53.

    Article  PubMed  Google Scholar 

  108. Gress TM, Lausser L, Schirra LR, et al. Combined microRNA and mRNA microfluidic TaqMan array cards for the diagnosis of malignancy of multiple types of pancreatico-biliary tumors in fine-needle aspiration material. Oncotarget. 2017;8:108223–37.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Rajamani D, Bhasin MK. Identification of key regulators of pancreatic cancer progression through multidimensional systems-level analysis. Genome Med. 2016;8:38.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

Hospital Management of the General Hospital of Western Theater Command (2021-XZYG-B16), the Sichuan Science and Technology Program (2022YFS0195). Pancreatic injury and repair Key laboratory of Sichuan Province (Grant no. 41732152).

Author information

Author notes

  1. Zhao Zhirong and Han Li have contributed equally to this work.

Authors and Affiliations

  1. General Surgery Center, General Hospital of Western Theater Command, No. 270, Rongdu Rd, **niu District, Chengdu, 610083, Sichuan, China

    Zhao Zhirong, Zhou Lichen & Dai Ruiwu

  2. College of Medicine, Southwest Jiaotong University, Chengdu, China

    Zhao Zhirong & Dai Ruiwu

  3. Ultrasound Medical Center, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, China

    Han Li

  4. School of Medicine, Jianghan University, Wuhan, 430056, Hubei, China

    Liu Yi

  5. Pancreatic Injury and Repair Key Laboratory of Sichuan Province, General Hospital of Western Theater Command, Chengdu, Sichuan, China

    Zhou Lichen & Dai Ruiwu

Authors
  1. Zhao Zhirong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Han Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liu Yi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhou Lichen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dai Ruiwu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: Zhirong Zhao and Li Han; formal analysis and investigation: Zhirong Zhao and Yi Liu; writing—original draft preparation: Zhirong Zhao, Li Han and Lichen Zhou; writing—review and editing: Ruiwu Dai; supervision: Ruiwu Dai.

Corresponding author

Correspondence to Dai Ruiwu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interests.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhirong, Z., Li, H., Yi, L. et al. Ferroptosis in pancreatic diseases: potential opportunities and challenges that require attention. Human Cell 36, 1233–1243 (2023). https://doi.org/10.1007/s13577-023-00894-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-023-00894-7

Keywords

Search

Navigation