TLR4 interaction with PIEZO1 facilitates the 5-HT-mediated intestinal motility dysfunction in offspring mice induced by LPS exposure during pregnancy
Several factors during pregnancy, such as changes in serotonin (5-HT) levels, can affect intestinal function in offspring mice. The role of 5-HT in regulating intestinal motility after lipopolysaccharide (LPS) exposure during pregnancy is unclear. In this study, Tlr4fl/fl and Tlr4▵IEC mice were inje...
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KeAi Communications Co., Ltd.
2025-09-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304225001965 |
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| author | Ruifang Luo Yuan Miao Riqiang Hu Fang Lin Junyan Yan Ting Yang Lu Xiao Zhujun Sun Yuting Wang Jie Chen |
| author_facet | Ruifang Luo Yuan Miao Riqiang Hu Fang Lin Junyan Yan Ting Yang Lu Xiao Zhujun Sun Yuting Wang Jie Chen |
| author_sort | Ruifang Luo |
| collection | DOAJ |
| description | Several factors during pregnancy, such as changes in serotonin (5-HT) levels, can affect intestinal function in offspring mice. The role of 5-HT in regulating intestinal motility after lipopolysaccharide (LPS) exposure during pregnancy is unclear. In this study, Tlr4fl/fl and Tlr4▵IEC mice were injected with LPS or phosphate-buffered saline during pregnancy to obtain prenatal LPS-exposed or non-exposed offspring mice. Changes in intestinal morphology, motility, and the TLR4 and 5-HT signaling pathways were examined in male offspring mice. The role of TLR4 in regulating 5-HT secretion was investigated in the BON-1 enterochromaffin cell line. In the prenatal LPS-exposed Tlr4fl/fl group, offspring mice exhibited colonic mucosal injury and faster intestinal motility, but these effects were absent when TLR4 was knocked out in intestinal epithelial cells. The TLR4 and 5-HT signaling pathways were activated in the colon of prenatal LPS-exposed Tlr4fl/fl offspring mice but were inactivated in prenatal LPS-exposed Tlr4 knockout offspring mice. In BON-1 cells, TLR4 interacted with the calcium ion channel PIEZO1, causing calcium influx and promoting 5-HT secretion. This process was disrupted by the TLR4 inhibitor TAK242. LPS exposure during pregnancy affected intestinal motility in offspring mice by activating TLR4 pathways in the colon and increasing 5-HT secretion from enterochromaffin cells. The effects of LPS on the intestine might be explained by the interaction between TLR4 and PIEZO1, suggesting that TLR4 is related to abnormal intestinal motility in offspring mice exposed to LPS during pregnancy. |
| format | Article |
| id | doaj-art-655523b05d0e47e2be48386dfe8fddbc |
| institution | Kabale University |
| issn | 2352-3042 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | KeAi Communications Co., Ltd. |
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| series | Genes and Diseases |
| spelling | doaj-art-655523b05d0e47e2be48386dfe8fddbc2025-08-20T03:29:18ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422025-09-0112510170710.1016/j.gendis.2025.101707TLR4 interaction with PIEZO1 facilitates the 5-HT-mediated intestinal motility dysfunction in offspring mice induced by LPS exposure during pregnancyRuifang Luo0Yuan Miao1Riqiang Hu2Fang Lin3Junyan Yan4Ting Yang5Lu Xiao6Zhujun Sun7Yuting Wang8Jie Chen9Growth, Development and Mental Health Center of Children and Adolescents, Children’s Hospital of Chongqing Medical University, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 404100, ChinaGrowth, Development and Mental Health Center of Children and Adolescents, Children’s Hospital of Chongqing Medical University, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 404100, ChinaGrowth, Development and Mental Health Center of Children and Adolescents, Children’s Hospital of Chongqing Medical University, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 404100, ChinaGrowth, Development and Mental Health Center of Children and Adolescents, Children’s Hospital of Chongqing Medical University, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 404100, ChinaGrowth, Development and Mental Health Center of Children and Adolescents, Children’s Hospital of Chongqing Medical University, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 404100, ChinaGrowth, Development and Mental Health Center of Children and Adolescents, Children’s Hospital of Chongqing Medical University, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 404100, ChinaDigestive Department, Children’s Hospital of Chongqing Medical University, Chongqing 404100, ChinaGrowth, Development and Mental Health Center of Children and Adolescents, Children’s Hospital of Chongqing Medical University, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 404100, ChinaDigestive Department, Children’s Hospital of Chongqing Medical University, Chongqing 404100, China; Corresponding author.Growth, Development and Mental Health Center of Children and Adolescents, Children’s Hospital of Chongqing Medical University, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 404100, China; Corresponding author.Several factors during pregnancy, such as changes in serotonin (5-HT) levels, can affect intestinal function in offspring mice. The role of 5-HT in regulating intestinal motility after lipopolysaccharide (LPS) exposure during pregnancy is unclear. In this study, Tlr4fl/fl and Tlr4▵IEC mice were injected with LPS or phosphate-buffered saline during pregnancy to obtain prenatal LPS-exposed or non-exposed offspring mice. Changes in intestinal morphology, motility, and the TLR4 and 5-HT signaling pathways were examined in male offspring mice. The role of TLR4 in regulating 5-HT secretion was investigated in the BON-1 enterochromaffin cell line. In the prenatal LPS-exposed Tlr4fl/fl group, offspring mice exhibited colonic mucosal injury and faster intestinal motility, but these effects were absent when TLR4 was knocked out in intestinal epithelial cells. The TLR4 and 5-HT signaling pathways were activated in the colon of prenatal LPS-exposed Tlr4fl/fl offspring mice but were inactivated in prenatal LPS-exposed Tlr4 knockout offspring mice. In BON-1 cells, TLR4 interacted with the calcium ion channel PIEZO1, causing calcium influx and promoting 5-HT secretion. This process was disrupted by the TLR4 inhibitor TAK242. LPS exposure during pregnancy affected intestinal motility in offspring mice by activating TLR4 pathways in the colon and increasing 5-HT secretion from enterochromaffin cells. The effects of LPS on the intestine might be explained by the interaction between TLR4 and PIEZO1, suggesting that TLR4 is related to abnormal intestinal motility in offspring mice exposed to LPS during pregnancy.http://www.sciencedirect.com/science/article/pii/S23523042250019655-HTEnterochromaffin cellIntestinal motilityPrenatal LPS exposureTLR4 |
| spellingShingle | Ruifang Luo Yuan Miao Riqiang Hu Fang Lin Junyan Yan Ting Yang Lu Xiao Zhujun Sun Yuting Wang Jie Chen TLR4 interaction with PIEZO1 facilitates the 5-HT-mediated intestinal motility dysfunction in offspring mice induced by LPS exposure during pregnancy Genes and Diseases 5-HT Enterochromaffin cell Intestinal motility Prenatal LPS exposure TLR4 |
| title | TLR4 interaction with PIEZO1 facilitates the 5-HT-mediated intestinal motility dysfunction in offspring mice induced by LPS exposure during pregnancy |
| title_full | TLR4 interaction with PIEZO1 facilitates the 5-HT-mediated intestinal motility dysfunction in offspring mice induced by LPS exposure during pregnancy |
| title_fullStr | TLR4 interaction with PIEZO1 facilitates the 5-HT-mediated intestinal motility dysfunction in offspring mice induced by LPS exposure during pregnancy |
| title_full_unstemmed | TLR4 interaction with PIEZO1 facilitates the 5-HT-mediated intestinal motility dysfunction in offspring mice induced by LPS exposure during pregnancy |
| title_short | TLR4 interaction with PIEZO1 facilitates the 5-HT-mediated intestinal motility dysfunction in offspring mice induced by LPS exposure during pregnancy |
| title_sort | tlr4 interaction with piezo1 facilitates the 5 ht mediated intestinal motility dysfunction in offspring mice induced by lps exposure during pregnancy |
| topic | 5-HT Enterochromaffin cell Intestinal motility Prenatal LPS exposure TLR4 |
| url | http://www.sciencedirect.com/science/article/pii/S2352304225001965 |
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