MEHP promotes liver fibrosis by down-regulating STAT5A in BRL-3A hepatocytes.

Abstract

OBJECTIVE:

As an environmental endocrine disruptor, mono-2-ethylhexyl phthalate (MEHP) can interfere with liver metabolism and lead to liver diseases. We aimed to investigate the role of MEHP in liver fibrosis and its molecular mechanism.

METHODS:

BRL-3A hepatocytes were exposed to MEHP (0, 10, 50, 100 and 200 μM) for 24 h. STAT5A gene was overexpressed by lentivirus transfection. The reactive oxygen species (ROS) was tested by the flow cytometer. The malondialdehyde (MDA), glutathione peroxidase (GSH-PX), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were detected by commercial kits. Real-Time PCR and Western blot were performed to test the relative mRNA and proteins levels, respectively.

RESULTS:

MEHP exposure significantly induced oxidative damage in BRL-3A cells, which inhibited the expression of STAT5A and promoted the expression of fibrosis related proteins MMP2, MMP9, TIMP2 and CTGF. After over-expression of STAT5A gene in BRL-3A cells, the elevated expression levels of CTGF, MMP2, MMP9 and TIMP2 induced by MEHP exposure were significantly reversed.

CONCLUSION:

This study demonstrated that MEHP exposure inhibited the expression of STAT5A by causing oxidative damage in BRL-3A hepatocytes, thus accelerating the expression of key molecules in fibrosis and promoting the occurrence of liver fibrosis.

• Authors: Yuezhu Zhang, Ju Hui, Yan Xu, Yingying Ma, Zhe Sun, Meng Zhang, Lushuang Nie, Lin Ye
• Journal: Chemosphere (Chemosphere) Vol. 295 Pg. 133925 (May 2022) ISSN: 1879-1298 [Electronic] England
• PMID: 35143864 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier Ltd. All rights reserved.

Chemical References

• STAT5 Transcription Factor
• Stat5a protein, rat
• Tumor Suppressor Proteins
• Diethylhexyl Phthalate
• mono-(2-ethylhexyl)phthalate

Topics

• Animals
• Diethylhexyl Phthalate (analogs & derivatives, metabolism)
• Hepatocytes (metabolism)
• Liver Cirrhosis (chemically induced)
• Oxidative Stress
• Rats
• STAT5 Transcription Factor (genetics, metabolism)
• Tumor Suppressor Proteins