MicroRNA-210 Promotes Bile Acid-Induced Cholestatic Liver Injury by Targeting Mixed-Lineage Leukemia-4 Methyltransferase in Mice.

ABSTRACT:

Background and aims

Bile acids (BAs) are important regulators of metabolism and energy balance, but excess BAs cause cholestatic liver injury. The histone methyltransferase mixed-lineage leukemia-4 (MLL4) is a transcriptional coactivator of the BA-sensing nuclear receptor farnesoid X receptor (FXR) and epigenetically up-regulates FXR targets important for the regulation of BA levels, small heterodimer partner (SHP), and bile salt export pump (BSEP). MLL4 expression is aberrantly down-regulated and BA homeostasis is disrupted in cholestatic mice, but the underlying mechanisms are unclear.

Approach and results

We examined whether elevated microRNA-210 (miR-210) in cholestatic liver promotes BA-induced pathology by inhibiting MLL4 expression. miR-210 was the most highly elevate

SUBMITTER: Kim YC 

PROVIDER: S-EPMC7089843 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature