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Progression of Repair and Injury in Human Liver Slices

1
Human Translational Models LLC, Irvine, CA 92612, USA
2
Inova Translational Medicine Institute, Inova Hospital, Fairfax, VA 22031, USA
3
Vitron, Inc., Tucson, AZ 85747, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(12), 4130; https://doi.org/10.3390/ijms19124130
Received: 30 October 2018 / Revised: 3 December 2018 / Accepted: 18 December 2018 / Published: 19 December 2018
(This article belongs to the Special Issue Liver Damage and Repair)
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Abstract

Human liver slice function was stressed by daily dosing of acetaminophen (APAP) or diclofenac (DCF) to investigate injury and repair. Initially, untreated human liver and kidney slices were evaluated with the global human U133A array to assess the extended culture conditions. Then, drug induced injury and signals of repair in human liver slices exposed to APAP or DCF (1 mM) were evaluated via specific gene expression arrays. In culture, the untreated human liver and kidney slices remained differentiated and gene expression indicated that repair pathways were activated in both tissues. Morphologically the human liver slices exhibited evidence of repair and regeneration, while kidney slices did not. APAP and DCF exposure caused a direct multi-factorial response. APAP and DCF induced gene expression changes in transporters, oxidative stress and mitochondria energy. DCF caused a greater effect on heat shock and endoplasmic reticulum (ER) stress gene expression. Concerning wound repair, APAP caused a mild repression of gene expression; DCF suppressed the expression of matrix collagen genes, the remodeling metalloproteases, cell adhesion integrins, indicating a greater hinderance to wound repair than APAP. Thus, human liver slices are a relevant model to investigate the mechanisms of drug-induced injury and repair. View Full-Text
Keywords: repair and injury; human liver slices repair and injury; human liver slices
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Vickers, A.E.M.; Ulyanov, A.V.; Fisher, R.L. Progression of Repair and Injury in Human Liver Slices. Int. J. Mol. Sci. 2018, 19, 4130.

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