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Search: onr:"swepub:oai:DiVA.org:his-13566" > MicroRNA-122 :

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  • Kia, RichardUniv Liverpool, Dept Mol & Clin Pharmacol, MRC Ctr Drug Safety Sci, Liverpool, England (author)

MicroRNA-122 : a novel hepatocyte-enriched in vitro marker of drug-induced cellular toxicity

  • Article/chapterEnglish2015

Publisher, publication year, extent ...

  • 2014-12-18
  • Oxford University Press,2015
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:his-13566
  • https://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-13566URI
  • https://doi.org/10.1093/toxsci/kfu269DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Emerging hepatic models for the study of drug-induced toxicity include pluripotent stem cell-derived hepatocyte-like cells (HLCs) and complex hepatocyte-non-parenchymal cellular coculture to mimic the complex multicellular interactions that recapitulate the niche environment in the human liver. However, a specific marker of hepatocyte perturbation, required to discriminate hepatocyte damage from non-specific cellular toxicity contributed by non-hepatocyte cell types or immature differentiated cells is currently lacking, as the cytotoxicity assays routinely used in in vitro toxicology research depend on intracellular molecules which are ubiquitously present in all eukaryotic cell types. In this study, we demonstrate that microRNA-122 (miR-122) detection in cell culture media can be used as a hepatocyte-enriched in vitro marker of drug-induced toxicity in homogeneous cultures of hepatic cells, and a cell-specific marker of toxicity of hepatic cells in heterogeneous cultures such as HLCs generated from various differentiation protocols and pluripotent stem cell lines, where conventional cytotoxicity assays using generic cellular markers may not be appropriate. We show that the sensitivity of the miR-122 cytotoxicity assay is similar to conventional assays that measure lactate dehydrogenase activity and intracellular adenosine triphosphate when applied in hepatic models with high levels of intracellular miR-122, and can be multiplexed with other assays. MiR-122 as a biomarker also has the potential to bridge results in in vitro experiments to in vivo animal models and human samples using the same assay, and to link findings from clinical studies in determining the relevance of in vitro models being developed for the study of drug-induced liver injury.

Subject headings and genre

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  • Kelly, LornaUniv Liverpool, Dept Mol & Clin Pharmacol, England / Stem Cells Safer Med, London, England (author)
  • Sison-Young, Rowena L. C.Univ Liverpool, Dept Mol & Clin Pharmacol, MRC Ctr Drug Safety Sci, Liverpool, England (author)
  • Zhang, FangUniv Liverpool, Dept Mol & Clin Pharmacol, England / Stem Cells Safer Med, London, England (author)
  • Pridgeon, Chris S.Univ Liverpool, Dept Mol & Clin Pharmacol, England / Stem Cells Safer Med, London, England (author)
  • Heslop, James A.Univ Liverpool, Dept Mol & Clin Pharmacol, MRC Ctr Drug Safety Sci, Liverpool, England (author)
  • Metcalfe, PeteUniv Liverpool, Dept Mol & Clin Pharmacol, MRC Ctr Drug Safety Sci, Liverpool, England (author)
  • Kitteringham, Neil R.Univ Liverpool, Dept Mol & Clin Pharmacol, England / Stem Cells Safer Med, London, England (author)
  • Baxter, MelissaUniv Manchester, Fac Life Sci, Manchester, England / Univ Cent Lancashire, Sch Med & Dent, Preston, England (author)
  • Harrison, SeanStem Cells Safer Med, London, England / Acad Hlth Sci Ctr, Fac Med & Human Sci, Ctr Endocrinol & Diabet,Inst Human Dev, Manchester, England (author)
  • Hanley, Neil A.Stem Cells Safer Med, London, England / Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Med & Human Sci, Ctr Endocrinol & Diabet,Inst Human Dev, Manchester, England / Cent Manchester Univ Hosp NHS Fdn Trust, Endocrinol Dept, Manchester England (author)
  • Burke, Zoe D.Stem Cells Safer Med, London, England / Univ Bath, Dept Biol & Biochem, Ctr Regenerat Med, Bath, England (author)
  • Storm,, Mike P.Stem Cells Safer Med, London, England / Univ Bath, Dept Biol & Biochem, Ctr Regenerat Med, Bath, England (author)
  • Welham, Melanie J.Univ Bath, Dept Biol & Biochem, Ctr Regenerat Med, Bath, England (author)
  • Tosh, DavidStem Cells Safer Med, London, England / Univ Bath, Dept Biol & Biochem, Ctr Regenerat Med, Bath, England (author)
  • Küppers-Munther, BarbaraHögskolan i Skövde,Institutionen för biovetenskap,Forskningscentrum för Systembiologi,Takara Bio Europe AB, Gothenburg, Sweden(Swepub:his)kupb (author)
  • Edsbagge, JosefinaTakara Bio Europe AB, Gothenburg, Sweden (author)
  • Lewis, Philip J. StarkeyUniv Edinburgh, MRC Ctr Regenerat Med, Edinburgh EH16 4UU, Midlothian, Scotland (author)
  • Bonner, FrankStem Cells Safer Med, London, England (author)
  • Harpur, ErnieStem Cells Safer Med, London, England / Newcastle Univ, Inst Cellular Med, Sch Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England (author)
  • Sidaway, JamesUniv Edinburgh, MRC Ctr Regenerat Med, Edinburgh EH16 4UU, Midlothian, Scotland / AstraZeneca R&D, Drug Safety & Metab, Cheshire, England (author)
  • Bowes, JoanneUniv Edinburgh, MRC Ctr Regenerat Med, Edinburgh EH16 4UU, Midlothian, Scotland / AstraZeneca R&D, Drug Safety & Metab, Cheshire, England (author)
  • Fenwick, Stephen W.Aintree Univ Hosp NHS Fdn Trust, North Western Hepatobiliary Unit, Liverpool, England (author)
  • Malik, HassanAintree Univ Hosp NHS Fdn Trust, North Western Hepatobiliary Unit, Liverpool, England (author)
  • Goldring, Chris E. P.Univ Liverpool, Dept Mol & Clin Pharmacol, MRC Ctr Drug Safety Sci, Liverpool, England / Stem Cells Safer Med, London England (author)
  • Park, B. KevinUniv Liverpool, Dept Mol & Clin Pharmacol, MRC Ctr Drug Safety Sci, Liverpool, England / Stem Cells Safer Med, London, England (author)
  • Univ Liverpool, Dept Mol & Clin Pharmacol, MRC Ctr Drug Safety Sci, Liverpool, EnglandUniv Liverpool, Dept Mol & Clin Pharmacol, England / Stem Cells Safer Med, London, England (creator_code:org_t)

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  • In:Toxicological Sciences: Oxford University Press144:1, s. 173-1851096-60801096-0929

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