Iron and liver fibrosis: mechanistic and clinical aspects

Journal article


Mehta, K, Farnaud, S and Sharp, P A (2019). Iron and liver fibrosis: mechanistic and clinical aspects. World Journal of Gastroenterology. 25 (5), pp. 521-538. https://doi.org/10.3748/wjg.v25.i5.521
AuthorsMehta, K, Farnaud, S and Sharp, P A
Abstract

Liver fibrosis is characterised by excessive deposition of extracellular matrix that interrupts normal liver functionality. It is a pathological stage in several untreated chronic liver diseases such as the iron overload syndrome hereditary haemochromatosis, viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis and diabetes. Interestingly, regardless of the aetiology, iron-loading is frequently observed in chronic liver diseases. Excess iron can feed the Fenton reaction to generate unquenchable amounts of free radicals that cause grave cellular and tissue damage and thereby contribute to fibrosis. Moreover, excess iron can induce fibrosis-promoting signals in the parenchymal and non-parenchymal cells, which accelerate disease progression and exacerbate liver pathology. Fibrosis regression is achievable following treatment, but if untreated or unsuccessful, it can progress to the irreversible cirrhotic stage leading to organ failure and hepatocellular carcinoma, where resection or transplantation remain the only curative options. Therefore, understanding the role of iron in liver fibrosis is extremely essential as it can help in formulating iron-related diagnostic, prognostic and treatment strategies. These can be implemented in isolation or in combination with the current approaches to prepone detection, and halt or decelerate fibrosis progression before it reaches the irreparable stage. Thus, this review narrates the role of iron in liver fibrosis. It examines the underlying mechanisms by which excess iron can facilitate fibrotic responses. It describes the role of iron in various clinical pathologies and lastly, highlights the significance and potential of iron-related proteins in the diagnosis and therapeutics of liver fibrosis.

Year2019
JournalWorld Journal of Gastroenterology
Journal citation25 (5), pp. 521-538
PublisherBaishideng Publishing Group
ISSN1007-9327
Digital Object Identifier (DOI)https://doi.org/10.3748/wjg.v25.i5.521
Publication dates
Print07 Feb 2019
Publication process dates
Deposited12 Feb 2019
Accepted07 Feb 2019
Accepted author manuscript
License
File Access Level
Open
Permalink -

https://openresearch.lsbu.ac.uk/item/867v9

Download files


Accepted author manuscript
Iron and liver fibrosis- mechanistic and clinical aspects.docx
License: CC BY-NC-ND 4.0
File access level: Open

  • 63
    total views
  • 44
    total downloads
  • 2
    views this month
  • 0
    downloads this month

Export as

Related outputs

A Novel Human Neuronal Cell Model to Study Iron Accumulation in Parkinson’s Disease
Mehta, K, Ahmed, B and Farnaud, S (2019). A Novel Human Neuronal Cell Model to Study Iron Accumulation in Parkinson’s Disease. Journal of Alzheimers Disease & Parkinsonism. 9 (1), p. 461. https://doi.org/10.4172/2161-0460.1000461
Measurement of 4-hydroxynonenal (4-HNE) protein adducts by ELISA
Mehta, K and Patel, V (2019). Measurement of 4-hydroxynonenal (4-HNE) protein adducts by ELISA. in: Hancock, John and Conway, Myra (ed.) Redox-Mediated Signal Transduction: Methods and Protocols, Methods in Molecular Biology, vol. 1990 Springer.
Betaine, in context.
Mehta, K and Patel, V (2015). Betaine, in context. in: Preedy, V (ed.) Betaine: Chemistry, Analysis, Function and Effects The Royal Society of Chemistry.
Molecular and cellular insights into iron regulation
Mehta, K (2012). Molecular and cellular insights into iron regulation. PhD Thesis University of Westminster School of Life Sciences
Molecular Effects of Alcohol on Iron Metabolism
Mehta, K, Farnaud, S and Patel, VB (2016). Molecular Effects of Alcohol on Iron Metabolism. in: Molecular Aspects of Alcohol and Nutrition: A Volume in the Molecular Nutrition Series Academic Press. pp. 355-368
Oxidative Stress in Iron-toxicity of Liver
Mehta, K (2018). Oxidative Stress in Iron-toxicity of Liver. in: Patel, V (ed.) The Liver: Oxidative stress and dietary antioxidants Elsevier. pp. 43-54
Characterisation of hepcidin response to holotransferrin treatment in CHO TRVb-1 cells
Mehta, K, Greenwell, P, Renshaw, D, Busbridge, M, Garcia, M, Farnaud, S and Patel, VB (2015). Characterisation of hepcidin response to holotransferrin treatment in CHO TRVb-1 cells. Blood Cells, Molecules, and Diseases. 55 (2), pp. 110-118. https://doi.org/10.1016/j.bcmd.2015.05.002
Iron Enhances Hepatic Fibrogenesis and Activates Transforming Growth Factor-β Signaling in Murine Hepatic Stellate Cells.
Mehta, K, Coombes, JD, Briones-Orta, M, Manka, PP, Williams, R., Patel, VB and Syn, W-K (2018). Iron Enhances Hepatic Fibrogenesis and Activates Transforming Growth Factor-β Signaling in Murine Hepatic Stellate Cells. American Journal of the Medical Sciences. 355 (2), pp. 183-190. https://doi.org/10.1016/j.amjms.2017.08.012
Case Studies: Effects of Beef, Whey and Carbohydrate Supplementation in Female Master Triathletes
Mehta, K, Seijo, M, Larumbe-Zabala, E, Ashrafi, N, Christides, T, Karsten, B, Nielsen, BV and Naclerio, F (2018). Case Studies: Effects of Beef, Whey and Carbohydrate Supplementation in Female Master Triathletes. Journal of Human Sport and Exercise. 14 (1), pp. 170-184. https://doi.org/10.14198/jhse.2019.141.14
HFE mRNA expression is responsive to intracellular and extracellular iron loading: short communication
Mehta, K, Farnaud, S and Patel, VB (2017). HFE mRNA expression is responsive to intracellular and extracellular iron loading: short communication. Molecular Biology Reports. 44 (5), pp. 399-403. https://doi.org/10.1007/s11033-017-4123-2
Erratum to: HFE mRNA expression is responsive to intracellular and extracellular iron loading: short communication
Mehta, K, Farnaud, S and Patel, VB (2017). Erratum to: HFE mRNA expression is responsive to intracellular and extracellular iron loading: short communication. Molecular Biology Reports. 44 (5), pp. 405-405. https://doi.org/10.1007/s11033-017-4127-y
Mucosa-associated invariant T cells link intestinal immunity with antibacterial immune defects in alcoholic liver disease
Riva, A, Patel, V, Kurioka, A, Jeffery, HC, Wright, G, Tarff, S, Shawcross, D, Ryan, JM, Evans, A, Azarian, S, Bajaj, JS, Fagan, A, Patel, V, Mehta, K, Lopez, C, Simonova, M, Katzarov, K, Hadzhiolova, T, Pavlova, S, Wendon, JA, Oo, YH, Klenerman, P, Williams, R. and Chokshi, S (2017). Mucosa-associated invariant T cells link intestinal immunity with antibacterial immune defects in alcoholic liver disease. Gut. Williams, R. (5), pp. 918-930. https://doi.org/10.1136/gutjnl-2017-314458
Characterization of hepcidin response to holotransferrin in novel recombinant TfR1 HepG2 cells
Mehta, K, Busbridge, M, Renshaw, D, Evans, RW, Farnaud, S and Patel, VB (2016). Characterization of hepcidin response to holotransferrin in novel recombinant TfR1 HepG2 cells. Blood Cells, Molecules, and Diseases. 61, pp. 37-45. https://doi.org/10.1016/j.bcmd.2016.06.008
Thyroid Hormone Receptor (TR): a regulator in Liver Fibrogenesis
Manka, P, Coombes, JD, Bechmann, L, Swiderska-Syn, M, Reid, D, Claridge, LC, Younis, R, Mehta, K, Briones, MA, Kitamura, N, Mi, Z, Kuo, PC, Williams, R., Eksteen, B, Diehl, AM, Gerken, G, Canbay, A, Flamant, F, Gauthier, K and Syn, WK (2016). Thyroid Hormone Receptor (TR): a regulator in Liver Fibrogenesis. Fibrogenesis. New York 01 - 02 Jan 2016 https://doi.org/10.1055/s-0036-1597375