MicroRNA 122 Reflects Liver Injury in Children with Intestinal Failure-Associated Liver Disease Treated with Intravenous Fish Oil.
Biomarkers
/ blood
Child, Preschool
Cholestasis
/ therapy
Female
Fish Oils
/ administration & dosage
Humans
Infant
Intestinal Diseases
/ complications
Liver Diseases
/ blood
Liver Function Tests
Male
MicroRNAs
/ blood
Parenteral Nutrition
/ adverse effects
Prospective Studies
Sequence Analysis, RNA
Soybean Oil
/ adverse effects
Journal
The Journal of nutrition
ISSN: 1541-6100
Titre abrégé: J Nutr
Pays: United States
ID NLM: 0404243
Informations de publication
Date de publication:
01 05 2020
01 05 2020
Historique:
received:
12
06
2019
revised:
30
08
2019
accepted:
01
01
2020
pubmed:
20
2
2020
medline:
15
9
2020
entrez:
20
2
2020
Statut:
ppublish
Résumé
There is evidence that microRNA (MIR) 122 is a biomarker for various liver diseases in adults and children. To date, MIR122 has not been explored in children with intestinal failure-associated liver disease (IFALD, or hyperbilirubinemia associated with prolonged parenteral nutrition). This study's purpose was to investigate changes in plasma miR-122, correlate miR-122 with serum liver function tests and enzymes, and investigate changes in whole blood transcripts including miR-122 targets in a group of children with IFALD who received pure intravenous fish oil (FO) as a treatment for cholestasis. This was a prospective, observational study that enrolled children with IFALD who received intravenous FO (1 g/kg/d) and whose cholestasis resolved with FO. Plasma miR-122 was measured using reverse transcription-quantitative real-time PCR, and whole blood miR-122 targets were quantified using RNA sequencing. Fourteen subjects with median age 6 mo (IQR: 3-65 mo) were enrolled. RNA sequence data were available for 4 subjects. When compared with the start of FO, median miR-122 concentrations at 6 mo of FO therapy decreased [1.0 (IQR: 1.0-1.0) compared with 0.04 (IQR: 0.01-0.6), P = 0.009]. At the start of FO, miR-122 correlated with conjugated bilirubin (r = 0.56; P = 0.038). At ∼3 mo of FO, miR-122 correlated with conjugated bilirubin (r = 0.56; P = 0.045). Reactive oxygen species, heme metabolism, coagulation, adipogenesis, IL-6-Janus kinase-signal transducer and activator of transcription (JAK-STAT) 3, IL-2-STAT5, transforming growth factor-β, TNF-α, inflammatory response, mammalian target of rapamycin gene families (normalized enrichment scores < -1.4), and miR-122 target genes were significantly downregulated with FO. In this small cohort of young children with IFALD, miR-122 decreased with FO therapy and correlated with conjugated bilirubin. Key pathways involving oxidation, inflammation, cellular differentiation, and nutrient regulation were downregulated. Data from this study provide information about IFALD and FO. This trial was registered at www.clinicaltrials.gov as NCT00969332.
Sections du résumé
BACKGROUND
There is evidence that microRNA (MIR) 122 is a biomarker for various liver diseases in adults and children. To date, MIR122 has not been explored in children with intestinal failure-associated liver disease (IFALD, or hyperbilirubinemia associated with prolonged parenteral nutrition).
OBJECTIVES
This study's purpose was to investigate changes in plasma miR-122, correlate miR-122 with serum liver function tests and enzymes, and investigate changes in whole blood transcripts including miR-122 targets in a group of children with IFALD who received pure intravenous fish oil (FO) as a treatment for cholestasis.
METHODS
This was a prospective, observational study that enrolled children with IFALD who received intravenous FO (1 g/kg/d) and whose cholestasis resolved with FO. Plasma miR-122 was measured using reverse transcription-quantitative real-time PCR, and whole blood miR-122 targets were quantified using RNA sequencing.
RESULTS
Fourteen subjects with median age 6 mo (IQR: 3-65 mo) were enrolled. RNA sequence data were available for 4 subjects. When compared with the start of FO, median miR-122 concentrations at 6 mo of FO therapy decreased [1.0 (IQR: 1.0-1.0) compared with 0.04 (IQR: 0.01-0.6), P = 0.009]. At the start of FO, miR-122 correlated with conjugated bilirubin (r = 0.56; P = 0.038). At ∼3 mo of FO, miR-122 correlated with conjugated bilirubin (r = 0.56; P = 0.045). Reactive oxygen species, heme metabolism, coagulation, adipogenesis, IL-6-Janus kinase-signal transducer and activator of transcription (JAK-STAT) 3, IL-2-STAT5, transforming growth factor-β, TNF-α, inflammatory response, mammalian target of rapamycin gene families (normalized enrichment scores < -1.4), and miR-122 target genes were significantly downregulated with FO.
CONCLUSIONS
In this small cohort of young children with IFALD, miR-122 decreased with FO therapy and correlated with conjugated bilirubin. Key pathways involving oxidation, inflammation, cellular differentiation, and nutrient regulation were downregulated. Data from this study provide information about IFALD and FO. This trial was registered at www.clinicaltrials.gov as NCT00969332.
Identifiants
pubmed: 32072161
pii: S0022-3166(22)02132-0
doi: 10.1093/jn/nxaa001
pmc: PMC7198298
doi:
Substances chimiques
Biomarkers
0
Fish Oils
0
MIRN122 microRNA, human
0
MicroRNAs
0
Soybean Oil
8001-22-7
Banques de données
ClinicalTrials.gov
['NCT00969332']
Types de publication
Journal Article
Observational Study
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1144-1150Subventions
Organisme : NCATS NIH HHS
ID : KL2 TR001882
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD041230
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR000122
Pays : United States
Informations de copyright
Copyright © The Author(s) 2020.
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