Benzophenone-3 induced abnormal development of enteric nervous system in zebrafish through MAPK/ERK signaling pathway

• Published in: Chemosphere (Oxford) Vol. 280; p. 130670
• Main Authors: Wang, Jing, Meng, Xinyao, Feng, Chenzhao, Xiao, Jun, Zhao, Xiang, Xiong, Bo, Feng, Jiexiong
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2021
• Subjects: Benzophenone-3; Enteric nervous system; Hirschsprung disease; Signaling pathway; Zebrafish; RET; UV; GI; Benzophenone-3; DMSO; Zebrafish; ENCC; BP-3; DNT; ENS; PDB; Enteric nervous system; DEGs; Signaling pathway; Hirschsprung disease; HAND2; HSCR; ISH
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2021.130670

Hirschsprung disease (HSCR) is a congenital disease characterized by the absence of enteric neurons, which is derived from the failure of the proliferation, differentiation or migration of the enteric neural crest cells (ENCCs). HSCR is associated with multiple risk factors, including polygenic inheritance factors and environmental factors. Genetic studies have been extensively performed, whereas studies related to environmental factors remain insufficient. Benzophenone-3 (BP-3), one important component of the ultraviolet (UV) filters, has been proved to have cytotoxicity and neurotoxicity which might be associated with HSCR. In this study, we used zebrafish as a model to investigate the relationship between BP-3 exposure and the development of the enteric nervous system (ENS) in vivo. Embryos exposed to BP-3 showed an average of 46% reduction of the number of the enteric neurons number. Besides, the ENCCs specific markers (ret and hand2) were downregulated upon BP-3 exposure. Moreover, we identified potential targets of BP-3 through Network Pharmacology Analysis and Autodock and demonstrated that the attenuation of the MAPK/ERK signaling might be the potential mechanism underlying the inhibition of the ENS development by BP-3. Importantly, MAPK/ERK signaling agonist could be used to rescue the ENS defects of zebrafish induced by BP-3. Overall, we characterized the influence of BP-3 on ENS development in vivo and explored possible molecular mechanisms. [Display omitted] •BP-3 exposure induced reduction of enteric neurons and abnormal gastrointestinal physiology in zebrafish.•BP-3 suppressed ret and hand2 expression in zebrafish embryos.•Network Pharmacology Analysis and molecular docking simulation revealed potential interaction between BP-3 and MAPK/ERK signaling pathway.•BP-3 could impact the ENS development through inhibiting MAPK/ERK signaling pathway.•MAPK/ERK signaling agonist could partially rescue the ENS development defects induced by BP-3 exposure.