Unknown

Dataset Information

0

Relationship between differential hepatic microRNA expression and decreased hepatic cytochrome P450 3A activity in cirrhosis.


ABSTRACT:

Background and aim

Liver cirrhosis is associated with decreased hepatic cytochrome P4503A (CYP3A) activity but the pathogenesis of this phenomenon is not well elucidated. In this study, we examined if certain microRNAs (miRNA) are associated with decreased hepatic CYP3A activity in cirrhosis.

Methods

Hepatic CYP3A activity and miRNA microarray expression profiles were measured in cirrhotic (n=28) and normal (n=12) liver tissue. Hepatic CYP3A activity was measured via midazolam hydroxylation in human liver microsomes. Additionally, hepatic CYP3A4 protein concentration and the expression of CYP3A4 mRNA were measured. Analyses were conducted to identify miRNAs which were differentially expressed between two groups but also were significantly associated with lower hepatic CYP3A activity.

Results

Hepatic CYP3A activity in cirrhotic livers was 1.7-fold lower than in the normal livers (0.28 ± 0.06 vs. 0.47 ± 0.07mL* min(-1)*mg protein(-1) (mean ± SEM), P=0.02). Six microRNAs (miR-155, miR-454, miR-582-5p, let-7f-1*, miR-181d, and miR-500) had >1.2-fold increase in cirrhotic livers and also had significant negative correlation with hepatic CYP3A activity (range of r = -0.44 to -0.52, P <0.05). Notably, miR-155, a known regulator of liver inflammation, had the highest fold increase in cirrhotic livers (2.2-fold, P=4.16E-08) and significantly correlated with hepatic CYP3A activity (r=-0.50, P=0.017). The relative expression (2(-??Ct) mean ± SEM) of hepatic CYP3A4 mRNA was significantly higher in cirrhotic livers (21.76 ± 2.65 vs. 5.91 ± 1.29, P=2.04E-07) but their levels did not significantly correlate with hepatic CYP3A activity (r=-0.43, P=0.08).

Conclusion

The strong association between certain miRNAs, notably miR-155, and lower hepatic CYP3A activity suggest that altered miRNA expression may regulate hepatic CYP3A activity.

SUBMITTER: Vuppalanchi R 

PROVIDER: S-EPMC3772944 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

altmetric image

Publications

Relationship between differential hepatic microRNA expression and decreased hepatic cytochrome P450 3A activity in cirrhosis.

Vuppalanchi Raj R   Liang Tiebing T   Goswami Chirayu Pankaj CP   Nalamasu Rohit R   Li Lang L   Jones David D   Wei Rongrong R   Liu Wanqing W   Sarasani Vishal V   Janga Sarath Chandra SC   Chalasani Naga N  

PloS one 20130913 9


<h4>Background and aim</h4>Liver cirrhosis is associated with decreased hepatic cytochrome P4503A (CYP3A) activity but the pathogenesis of this phenomenon is not well elucidated. In this study, we examined if certain microRNAs (miRNA) are associated with decreased hepatic CYP3A activity in cirrhosis.<h4>Methods</h4>Hepatic CYP3A activity and miRNA microarray expression profiles were measured in cirrhotic (n=28) and normal (n=12) liver tissue. Hepatic CYP3A activity was measured via midazolam hyd  ...[more]

Similar Datasets

2013-08-15 | E-GEOD-49012 | biostudies-arrayexpress
2013-08-15 | GSE49012 | GEO
| S-EPMC3584707 | biostudies-literature
| S-EPMC6483910 | biostudies-literature
| S-EPMC4020009 | biostudies-literature
| S-EPMC4931891 | biostudies-literature
| S-EPMC3940493 | biostudies-literature
| S-EPMC9131896 | biostudies-literature
| PRJEB38781 | ENA