Nonylphenol exposure increases the risk of Hirschsprung’s disease by inducing macrophage M1 polarization
Nonylphenol (NP), a ubiquitous environmental contaminant used as a surfactant in industrial production and classified as an endocrine disruptor, could interfere hormone secretion and exhibit neurotoxicity in organisms. Hirschsprung’s disease (HSCR), one of the most frequently observed congenital mal...
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325000922 |
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| author | Xuefeng Yang Chengyan Tang Daiwei Zhu Xingrong Xia Qing Du Lu Huang Jianguo Liu Yuanmei Liu |
| author_facet | Xuefeng Yang Chengyan Tang Daiwei Zhu Xingrong Xia Qing Du Lu Huang Jianguo Liu Yuanmei Liu |
| author_sort | Xuefeng Yang |
| collection | DOAJ |
| description | Nonylphenol (NP), a ubiquitous environmental contaminant used as a surfactant in industrial production and classified as an endocrine disruptor, could interfere hormone secretion and exhibit neurotoxicity in organisms. Hirschsprung’s disease (HSCR), one of the most frequently observed congenital malformations of the digestive system, arises mainly due to the failure of enteric neural crest cells to migrate to the distal colon during embryonic development. However, the effects of NP exposure on HSCR are largely unknown. Herein, we identified the content of NP and expression of lncRNA LINC00294/Inhibin Subunit Beta E (INHBE) axis in clinical samples and evaluated the crucial role of lncRNA LINC00294/INHBE axis in the neurogenic potential of neurons and the neurotoxicity effects of NP in the SH-SY5Y cells and female specific pathogen-free (SPF) rat model. Our results showed that NP concentration and LINC00294 were significantly associated with HSCR occurrence and macrophage polarization in human HSCR specimens. Moreover, NP promoted macrophage M1 polarization. The proliferation and migration were weakened, and apoptosis was heightened by the conditioned medium of NP-treated macrophages in SH-SY5Y cells. Contrarily, LINC00294 overexpression and INHBE knockdown reversed the neurotoxicity effect of NP on SH-SY5Y cells. Furthermore, the neurotoxicity effect of NP was abolished by clodronate liposomes in the rat model. In conclusion, NP could induce macrophage M1 polarization via the LINC00294/INHBE axis and increase the risk of Hirschsprung’s disease. Our findings would provide a foundation for the toxicity study and risk assessments of NP. |
| format | Article |
| id | doaj-art-a0796646e38746cba20c0d7a0018b9dd |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-a0796646e38746cba20c0d7a0018b9dd2025-02-12T05:30:13ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01290117756Nonylphenol exposure increases the risk of Hirschsprung’s disease by inducing macrophage M1 polarizationXuefeng Yang0Chengyan Tang1Daiwei Zhu2Xingrong Xia3Qing Du4Lu Huang5Jianguo Liu6Yuanmei Liu7Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, China; Department of Pediatric Surgery, Guizhou Children Hospital, Zunyi, Guizhou 563000, China; Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, ChinaDepartment of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, China; Department of Pediatric Surgery, Guizhou Children Hospital, Zunyi, Guizhou 563000, ChinaDepartment of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, China; Department of Pediatric Surgery, Guizhou Children Hospital, Zunyi, Guizhou 563000, ChinaDepartment of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, China; Department of Pediatric Surgery, Guizhou Children Hospital, Zunyi, Guizhou 563000, ChinaDepartment of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, China; Department of Pediatric Surgery, Guizhou Children Hospital, Zunyi, Guizhou 563000, ChinaDepartment of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, China; Department of Pediatric Surgery, Guizhou Children Hospital, Zunyi, Guizhou 563000, ChinaKey Laboratory of Oral Disease Research, School of Stomatology, Zunyi Medical University, Zunyi, Guizhou 563000, China; Corresponding author.Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, China; Department of Pediatric Surgery, Guizhou Children Hospital, Zunyi, Guizhou 563000, China; Corresponding author at: Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, China.Nonylphenol (NP), a ubiquitous environmental contaminant used as a surfactant in industrial production and classified as an endocrine disruptor, could interfere hormone secretion and exhibit neurotoxicity in organisms. Hirschsprung’s disease (HSCR), one of the most frequently observed congenital malformations of the digestive system, arises mainly due to the failure of enteric neural crest cells to migrate to the distal colon during embryonic development. However, the effects of NP exposure on HSCR are largely unknown. Herein, we identified the content of NP and expression of lncRNA LINC00294/Inhibin Subunit Beta E (INHBE) axis in clinical samples and evaluated the crucial role of lncRNA LINC00294/INHBE axis in the neurogenic potential of neurons and the neurotoxicity effects of NP in the SH-SY5Y cells and female specific pathogen-free (SPF) rat model. Our results showed that NP concentration and LINC00294 were significantly associated with HSCR occurrence and macrophage polarization in human HSCR specimens. Moreover, NP promoted macrophage M1 polarization. The proliferation and migration were weakened, and apoptosis was heightened by the conditioned medium of NP-treated macrophages in SH-SY5Y cells. Contrarily, LINC00294 overexpression and INHBE knockdown reversed the neurotoxicity effect of NP on SH-SY5Y cells. Furthermore, the neurotoxicity effect of NP was abolished by clodronate liposomes in the rat model. In conclusion, NP could induce macrophage M1 polarization via the LINC00294/INHBE axis and increase the risk of Hirschsprung’s disease. Our findings would provide a foundation for the toxicity study and risk assessments of NP.http://www.sciencedirect.com/science/article/pii/S0147651325000922Hirschsprung’s diseaseNonylphenolNeurogenic potentialMacrophage M1 polarizationLncRNA LINC00294/INHBE axis |
| spellingShingle | Xuefeng Yang Chengyan Tang Daiwei Zhu Xingrong Xia Qing Du Lu Huang Jianguo Liu Yuanmei Liu Nonylphenol exposure increases the risk of Hirschsprung’s disease by inducing macrophage M1 polarization Ecotoxicology and Environmental Safety Hirschsprung’s disease Nonylphenol Neurogenic potential Macrophage M1 polarization LncRNA LINC00294/INHBE axis |
| title | Nonylphenol exposure increases the risk of Hirschsprung’s disease by inducing macrophage M1 polarization |
| title_full | Nonylphenol exposure increases the risk of Hirschsprung’s disease by inducing macrophage M1 polarization |
| title_fullStr | Nonylphenol exposure increases the risk of Hirschsprung’s disease by inducing macrophage M1 polarization |
| title_full_unstemmed | Nonylphenol exposure increases the risk of Hirschsprung’s disease by inducing macrophage M1 polarization |
| title_short | Nonylphenol exposure increases the risk of Hirschsprung’s disease by inducing macrophage M1 polarization |
| title_sort | nonylphenol exposure increases the risk of hirschsprung s disease by inducing macrophage m1 polarization |
| topic | Hirschsprung’s disease Nonylphenol Neurogenic potential Macrophage M1 polarization LncRNA LINC00294/INHBE axis |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325000922 |
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