Bisphenol A, an environmental estrogen-like toxic chemical, induces cardiac fibrosis by activating the ERK1/2 pathway.

Abstract

Bisphenol A (BPA) is a widely studied typical endocrine-disrupting chemical. The present study aimed to verify whether BPA could induce proliferation of cardiac fibroblasts and collagen production leading to cardiac interstitial fibrosis. After exposure to BPA for 30 consecutive days, decreased cardiac function was observed in rats using echocardiography, and the deposition of collagen was detected by Masson's trichrome staining and electron microscope. BPA remarkably stimulated proliferation and migration of cultured cardiac fibroblasts and collagen production in a concentration-dependent manner, as revealed by MTT, wound healing assay and collagen assay. Meanwhile, BPA treatment also enhanced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). In contrast, pretreatment with estrogen receptor inhibitor ICI182780 or ERK inhibitor PD98059 prevented the enhanced phosphorylation of ERK1/2, and subsequently inhibited the up-regulation of transforming growth factor-β1 (TGF-β1) expression induced by BPA. As a consequence, these inhibitors also decreased proliferation and collagen production, as well as the fibrosis-related genes expression. Taken together, our results indicated that BPA may act as a promoting factor in proliferative process and collagen production of cardiac fibroblasts via activating ERK1/2.

• Authors: Yingying Hu, Li Zhang, Xianxian Wu, Liangyu Hou, Zhange Li, Jin Ju, Qian Li, Wei Qin, Jiamin Li, Qingwei Zhang, Tong Zhou, Longyin Zhang, Chaoqian Xu, Zhiwei Fang, Yong Zhang
• Journal: Toxicology letters (Toxicol Lett) Vol. 250-251 Pg. 1-9 (May 27 2016) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 27025157 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Benzhydryl Compounds
• Endocrine Disruptors
• Environmental Pollutants
• Estrogen Antagonists
• Phenols
• Protein Kinase Inhibitors
• Tgfb1 protein, rat
• Transforming Growth Factor beta1
• Collagen
• Mapk1 protein, rat
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• bisphenol A

Topics

• Animals
• Benzhydryl Compounds (toxicity)
• Cardiomyopathies (chemically induced, enzymology, pathology, physiopathology)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Collagen (metabolism)
• Dose-Response Relationship, Drug
• Endocrine Disruptors (toxicity)
• Environmental Pollutants (toxicity)
• Enzyme Activation
• Estrogen Antagonists (pharmacology)
• Fibroblasts (drug effects, enzymology, ultrastructure)
• Fibrosis
• Mitogen-Activated Protein Kinase 1 (antagonists & inhibitors, metabolism)
• Mitogen-Activated Protein Kinase 3 (antagonists & inhibitors, metabolism)
• Myocardium (enzymology, ultrastructure)
• Phenols (toxicity)
• Phosphorylation
• Protein Kinase Inhibitors (pharmacology)
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Time Factors
• Transforming Growth Factor beta1 (metabolism)