Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis

Jeanine Ward; Chitra Kanchagar; Isana Veksler-Lublinsky; Rosalind C. Lee; Mitchell R. McGill; Hartmut Jaeschke; Steven C. Curry; Victor R. Ambros

doi:10.1073/pnas.1412608111

Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis

Jeanine Ward
, Chitra Kanchagar
, Isana Veksler-Lublinsky
, Rosalind C. Lee
, Mitchell R. McGill
, Hartmut Jaeschke
, Steven C. Curry
, Victor R. Ambros

Research output: Contribution to journal › Article › peer-review

158 Scopus citations

Abstract

We have identified, by quantitative real-time PCR, hundreds of miRNAs that are dramatically elevated in the plasma or serum of acetaminophen (APAP) overdose patients. Most of these circulating microRNAs decrease toward normal levels during treatment with N-acetyl cysteine (NAC). We identified a set of 11 miRNAs whose profiles and dynamics in the circulation during NAC treatment can discriminate APAP hepatotoxicity from ischemic hepatitis. The elevation of certain miRNAs can precede the dramatic rise in the standard biomarker, alanine aminotransferase (ALT), and these miRNAs also respond more rapidly than ALT to successful treatment. Our results suggest that miRNAs can serve as sensitive diagnostic and prognostic clinical tools for severe liver injury and could be useful for monitoring drug-induced liver injury during drug discovery.

Original language	English
Pages (from-to)	12169-12174
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	111
Issue number	33
DOIs	https://doi.org/10.1073/pnas.1412608111
State	Published - 19 Aug 2014
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

hsa-miR-122-5p
hsa-miR-3646-3p
hsa-miR-412

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.1412608111

Cite this

Ward, J., Kanchagar, C., Veksler-Lublinsky, I., Lee, R. C., McGill, M. R., Jaeschke, H., Curry, S. C., & Ambros, V. R. (2014). Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis. Proceedings of the National Academy of Sciences of the United States of America, 111(33), 12169-12174. https://doi.org/10.1073/pnas.1412608111

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title = "Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis",

abstract = "We have identified, by quantitative real-time PCR, hundreds of miRNAs that are dramatically elevated in the plasma or serum of acetaminophen (APAP) overdose patients. Most of these circulating microRNAs decrease toward normal levels during treatment with N-acetyl cysteine (NAC). We identified a set of 11 miRNAs whose profiles and dynamics in the circulation during NAC treatment can discriminate APAP hepatotoxicity from ischemic hepatitis. The elevation of certain miRNAs can precede the dramatic rise in the standard biomarker, alanine aminotransferase (ALT), and these miRNAs also respond more rapidly than ALT to successful treatment. Our results suggest that miRNAs can serve as sensitive diagnostic and prognostic clinical tools for severe liver injury and could be useful for monitoring drug-induced liver injury during drug discovery.",

keywords = "hsa-miR-122-5p, hsa-miR-3646-3p, hsa-miR-412",

author = "Jeanine Ward and Chitra Kanchagar and Isana Veksler-Lublinsky and Lee, \{Rosalind C.\} and McGill, \{Mitchell R.\} and Hartmut Jaeschke and Curry, \{Steven C.\} and Ambros, \{Victor R.\}",

year = "2014",

month = aug,

day = "19",

doi = "10.1073/pnas.1412608111",

language = "English",

volume = "111",

pages = "12169--12174",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

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Ward, J, Kanchagar, C, Veksler-Lublinsky, I, Lee, RC, McGill, MR, Jaeschke, H, Curry, SC & Ambros, VR 2014, 'Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis', Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 33, pp. 12169-12174. https://doi.org/10.1073/pnas.1412608111

Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis. / Ward, Jeanine; Kanchagar, Chitra; Veksler-Lublinsky, Isana et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 33, 19.08.2014, p. 12169-12174.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis

AU - Ward, Jeanine

AU - Kanchagar, Chitra

AU - Veksler-Lublinsky, Isana

AU - Lee, Rosalind C.

AU - McGill, Mitchell R.

AU - Jaeschke, Hartmut

AU - Curry, Steven C.

AU - Ambros, Victor R.

PY - 2014/8/19

Y1 - 2014/8/19

N2 - We have identified, by quantitative real-time PCR, hundreds of miRNAs that are dramatically elevated in the plasma or serum of acetaminophen (APAP) overdose patients. Most of these circulating microRNAs decrease toward normal levels during treatment with N-acetyl cysteine (NAC). We identified a set of 11 miRNAs whose profiles and dynamics in the circulation during NAC treatment can discriminate APAP hepatotoxicity from ischemic hepatitis. The elevation of certain miRNAs can precede the dramatic rise in the standard biomarker, alanine aminotransferase (ALT), and these miRNAs also respond more rapidly than ALT to successful treatment. Our results suggest that miRNAs can serve as sensitive diagnostic and prognostic clinical tools for severe liver injury and could be useful for monitoring drug-induced liver injury during drug discovery.

AB - We have identified, by quantitative real-time PCR, hundreds of miRNAs that are dramatically elevated in the plasma or serum of acetaminophen (APAP) overdose patients. Most of these circulating microRNAs decrease toward normal levels during treatment with N-acetyl cysteine (NAC). We identified a set of 11 miRNAs whose profiles and dynamics in the circulation during NAC treatment can discriminate APAP hepatotoxicity from ischemic hepatitis. The elevation of certain miRNAs can precede the dramatic rise in the standard biomarker, alanine aminotransferase (ALT), and these miRNAs also respond more rapidly than ALT to successful treatment. Our results suggest that miRNAs can serve as sensitive diagnostic and prognostic clinical tools for severe liver injury and could be useful for monitoring drug-induced liver injury during drug discovery.

KW - hsa-miR-122-5p

KW - hsa-miR-3646-3p

KW - hsa-miR-412

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U2 - 10.1073/pnas.1412608111

DO - 10.1073/pnas.1412608111

M3 - Article

C2 - 25092309

AN - SCOPUS:84906328202

SN - 0027-8424

VL - 111

SP - 12169

EP - 12174

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 33

ER -

Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis

Abstract

UN SDGs

Keywords

ASJC Scopus subject areas

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