Limits...
Circulating microRNAs Reveal Time Course of Organ Injury in a Porcine Model of Acetaminophen-Induced Acute Liver Failure.

Baker LA, Lee KC, Palacios Jimenez C, Alibhai H, Chang YM, Leckie PJ, Mookerjee RP, Davies NA, Andreola F, Jalan R - PLoS ONE (2015)

Bottom Line: The increase in miR124-1 occurred concurrent with the pre-terminal increase in intracranial pressure (P<0.0001) and was associated with decreasing cerebral perfusion pressure (P<0.002).Conclusions: MicroRNAs were released passively into the circulation in response to acetaminophen-induced cellular damage.A significant increase in global microRNA was detectable prior to significant increases in miR122, miR192 and miR124-1, which were associated with clinical evidence of liver, kidney and brain injury respectively.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Science and Services, Royal Veterinary College, Hatfield, Hertfordshire, United Kingdom.

ABSTRACT
Acute liver failure is a rare but catastrophic condition which can progress rapidly to multi-organ failure. Studies investigating the onset of individual organ injury such as the liver, kidneys and brain during the evolution of acute liver failure, are lacking. MicroRNAs are short, non-coding strands of RNA that are released into the circulation following tissue injury. In this study, we have characterised the release of both global microRNA and specific microRNA species into the plasma using a porcine model of acetaminophen-induced acute liver failure. Pigs were induced to acute liver failure with oral acetaminophen over 19h±2h and death occurred 13h±3h thereafter. Global microRNA concentrations increased 4h prior to acute liver failure in plasma (P<0.0001) but not in isolated exosomes, and were associated with increasing plasma levels of the damage-associated molecular pattern molecule, genomic DNA (P<0.0001). MiR122 increased around the time of onset of acute liver failure (P<0.0001) and was associated with increasing international normalised ratio (P<0.0001). MiR192 increased 8h after acute liver failure (P<0.0001) and was associated with increasing creatinine (P<0.0001). The increase in miR124-1 occurred concurrent with the pre-terminal increase in intracranial pressure (P<0.0001) and was associated with decreasing cerebral perfusion pressure (P<0.002). Conclusions: MicroRNAs were released passively into the circulation in response to acetaminophen-induced cellular damage. A significant increase in global microRNA was detectable prior to significant increases in miR122, miR192 and miR124-1, which were associated with clinical evidence of liver, kidney and brain injury respectively.

No MeSH data available.


Related in: MedlinePlus

Increasing global miRNA concentrations in plasma associate with parameters of clinical ALF progression.The global miRNA concentrations were compared to six time-matched parameters representing: liver injury; kidney injury; brain injury; acid-base imbalance; cardiovascular stability; vascular permeability. β: fixed effects; CI: confidence interval.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4446266&req=5

pone.0128076.g002: Increasing global miRNA concentrations in plasma associate with parameters of clinical ALF progression.The global miRNA concentrations were compared to six time-matched parameters representing: liver injury; kidney injury; brain injury; acid-base imbalance; cardiovascular stability; vascular permeability. β: fixed effects; CI: confidence interval.

Mentions: Plasma global miRNA levels (all RNA strands between 10 and 40 nucleotides in length), measured by electropherogram, increased with disease progression in APAP-treated animals, beginning 16h after the onset of APAP dosing and continuing until death (P < 0.0001, Fig 1). Global miRNA concentrations were significantly associated with all six markers of disease progression assessed (P < 0.0001; Fig 2)


Circulating microRNAs Reveal Time Course of Organ Injury in a Porcine Model of Acetaminophen-Induced Acute Liver Failure.

Baker LA, Lee KC, Palacios Jimenez C, Alibhai H, Chang YM, Leckie PJ, Mookerjee RP, Davies NA, Andreola F, Jalan R - PLoS ONE (2015)

Increasing global miRNA concentrations in plasma associate with parameters of clinical ALF progression.The global miRNA concentrations were compared to six time-matched parameters representing: liver injury; kidney injury; brain injury; acid-base imbalance; cardiovascular stability; vascular permeability. β: fixed effects; CI: confidence interval.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4446266&req=5

pone.0128076.g002: Increasing global miRNA concentrations in plasma associate with parameters of clinical ALF progression.The global miRNA concentrations were compared to six time-matched parameters representing: liver injury; kidney injury; brain injury; acid-base imbalance; cardiovascular stability; vascular permeability. β: fixed effects; CI: confidence interval.
Mentions: Plasma global miRNA levels (all RNA strands between 10 and 40 nucleotides in length), measured by electropherogram, increased with disease progression in APAP-treated animals, beginning 16h after the onset of APAP dosing and continuing until death (P < 0.0001, Fig 1). Global miRNA concentrations were significantly associated with all six markers of disease progression assessed (P < 0.0001; Fig 2)

Bottom Line: The increase in miR124-1 occurred concurrent with the pre-terminal increase in intracranial pressure (P<0.0001) and was associated with decreasing cerebral perfusion pressure (P<0.002).Conclusions: MicroRNAs were released passively into the circulation in response to acetaminophen-induced cellular damage.A significant increase in global microRNA was detectable prior to significant increases in miR122, miR192 and miR124-1, which were associated with clinical evidence of liver, kidney and brain injury respectively.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Science and Services, Royal Veterinary College, Hatfield, Hertfordshire, United Kingdom.

ABSTRACT
Acute liver failure is a rare but catastrophic condition which can progress rapidly to multi-organ failure. Studies investigating the onset of individual organ injury such as the liver, kidneys and brain during the evolution of acute liver failure, are lacking. MicroRNAs are short, non-coding strands of RNA that are released into the circulation following tissue injury. In this study, we have characterised the release of both global microRNA and specific microRNA species into the plasma using a porcine model of acetaminophen-induced acute liver failure. Pigs were induced to acute liver failure with oral acetaminophen over 19h±2h and death occurred 13h±3h thereafter. Global microRNA concentrations increased 4h prior to acute liver failure in plasma (P<0.0001) but not in isolated exosomes, and were associated with increasing plasma levels of the damage-associated molecular pattern molecule, genomic DNA (P<0.0001). MiR122 increased around the time of onset of acute liver failure (P<0.0001) and was associated with increasing international normalised ratio (P<0.0001). MiR192 increased 8h after acute liver failure (P<0.0001) and was associated with increasing creatinine (P<0.0001). The increase in miR124-1 occurred concurrent with the pre-terminal increase in intracranial pressure (P<0.0001) and was associated with decreasing cerebral perfusion pressure (P<0.002). Conclusions: MicroRNAs were released passively into the circulation in response to acetaminophen-induced cellular damage. A significant increase in global microRNA was detectable prior to significant increases in miR122, miR192 and miR124-1, which were associated with clinical evidence of liver, kidney and brain injury respectively.

No MeSH data available.


Related in: MedlinePlus