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Toxicol Lett. 2016 May 27;250-251:1-9. doi: 10.1016/j.toxlet.2016.03.008. Epub 2016 Mar 26.

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

Author information

1
Department of Pharmacology, State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin Medical University, Harbin 150081, China; Department of Pharmacy, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
2
Institute of Clinical Pharmacology, The Second Affiliated Hospital, Key Laboratory of Drug Research, Heilongjiang Higher Education Institutions, Harbin Medical University, Harbin 150086, China.
3
Department of Pharmacology, State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin Medical University, Harbin 150081, China.
4
Department of Pharmaceutical Analysis, College of Pharmacy, Harbin Medical University, Harbin 150081, China.
5
Department of Pharmacology, State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin Medical University, Harbin 150081, China; Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin 150086, China; Wu Lien-Teh lnstitute, Harbin Medical University, Harbin 150086, China. Electronic address: hmuzhangyong@hotmail.com.

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.

KEYWORDS:

Bisphenol A; Cardiac fibroblast; Cardiac fibrosis; Extracellular signal-regulated kinase 1/2

PMID:
27025157
DOI:
10.1016/j.toxlet.2016.03.008
[Indexed for MEDLINE]

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