MiRNA-145 is involved in the development of resistin-induced insulin resistance in HepG2 cells.

Abstract

BACKGROUND:

Resistin is associated with insulin resistance, and determining its developmental and molecular mechanisms may help the development of novel treatments. MicroRNAs (miRNAs) are involved in many physiological and pathological processes as negative regulators. However, it remains unclear whether miRNAs play a role in resistin-induced insulin resistance. We performed mouse liver miRNA microarrays to analyze the differences in expression between resistin-treated and control mice. Resistin upregulated miR-145 both in vivo and in vitro. Therefore, we aimed to study whether miR-145 played a role in resistin-induced insulin resistance.

METHODS AND RESULTS:

We transfected HepG2 cells, and used miR-145 mimics and inhibitors to assess the role of miR-145 in resistin-induced insulin resistance. The overexpression of miR-145 inhibited glucose uptake in HepG2 cells, diminished the phosphorylation of Akt and IRS-1, and induced insulin resistance in hepatocytes. Next, a study of transcriptional regulation revealed that p65 was essential for the upregulation of miR-145 by resistin, and chromatin immunoprecipitation (ChIP) confirmed that p65 could bind to the promoter region of miR-145.

CONCLUSION:

miR-145 plays a role in the development of resistin-induced insulin resistance via the p65 pathway.

• Authors: Fengyun Wen, Yi Yang, Dan Jin, Jun Sun, Xiaoling Yu, Zaiqing Yang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 445 Issue 2 Pg. 517-23 (Mar 07 2014) ISSN: 1090-2104 [Electronic] United States
• PMID: 24548410 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• IRS1 protein, human
• IRS2 protein, human
• Insulin Receptor Substrate Proteins
• MIRN145 microRNA, human
• MicroRNAs
• Resistin
• Transcription Factor RelA
• Glucose

Topics

• Animals
• Down-Regulation
• Glucose (metabolism)
• HEK293 Cells
• Hep G2 Cells (metabolism, pathology)
• Humans
• Insulin Receptor Substrate Proteins (genetics)
• Insulin Resistance (genetics, physiology)
• Male
• Mice
• Mice, Inbred C57BL
• MicroRNAs (genetics)
• Promoter Regions, Genetic
• Resistin (metabolism)
• Transcription Factor RelA (metabolism)
• Up-Regulation