{"title":"正常结肠赫氏病结肠上皮细胞 Claudin-4 和白三烯 B4 受体 2 对牵拉后小肠结肠炎的影响","authors":"Kumpei Abe, Masahiro Takeda, Asuka Ishiyama, Masahiro Shimizu, Hiroki Goto, Hisae Iida, Takashi Fujimoto, Eri Ueda-Abe, Shunsuke Yamada, Kentaro Fujiwara, Soichi Shibuya, Takanori Ochi, Rumi Arii, Yuta Yazaki, Go Miyano, Masahiko Urao, Tadaharu Okazaki, Hiroyuki Koga, Geoffrey J Lane, Atsuyuki Yamataka, Kazuto Suda","doi":"10.1016/j.jpedsurg.2024.161900","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>To investigate whether Leukotriene B4 receptor 2 (BLT-2), an upstream regulator of tight junction protein (TJP) Claudin-4, and TJPs could be etiologic factors in Hirschsprung-associated enterocolitis (HAEC) after pull-through (PT) for Hirschsprung disease (HD).</p><p><strong>Methods: </strong>Normoganglionic colon (HD-N) and aganglionic rectum (HD-A) specimens from rectal/rectosigmoid (R/RS) or descending/transverse (D/T) HD were assessed using quantitative polymerase chain reaction (qPCR) for Occludin, TJP-1, TJP-2, Junctional adhesion molecule (JAM)-1, JAM-2, Claudin-1, Claudin-3, Claudin-4, and BLT-2 and immunoblotting for Claudin-4 using fresh specimens obtained intraoperatively (2021-2024; n = 17; R/RS = 15 and D/T = 2). Claudin-4 immunohistochemistry was also evaluated quantitatively using preserved (n = 29; R/RS = 20 and D/T = 9; 2009-2021) and fresh HD specimens for comparison with anorectal malformation patients having colostomy closure as controls (n = 42) and between HD-A versus HD-N, R/RS versus D/T, and HAEC (+) versus HAEC (-). Technically inadequate or transitional zone PT were excluded.</p><p><strong>Results: </strong>Subjects were 123 PT cases. Mean ages at PT/colostomy closure (years) were R/RS: 2.7 ± 2.9, D/T: 1.6 ± 2.2, and controls: 1.4 ± 0.7. Postoperative HAEC occurred 18 times in 14 PT cases (grade I = 5, grade II = 13). Post-PT HAEC was significantly more frequent in D/T (50.0% versus 6.4%; p < 0.001); Claudin-4 was significantly lower in HD-N from post-PT HAEC cases, especially D/T (p < 0.05) on immunohistochemistry. Claudin-4 was significantly lower in HD-N/HD-A compared with controls on immunoblotting (p < 0.05) and immunohistochemistry (p < 0.001). qPCR showed TJP-1, TJP-2, JAM-1, JAM-2, Claudin-4, and BLT-2 were significantly lower in HD-N/HD-A compared with controls.</p><p><strong>Conclusions: </strong>Lower Claudin-4 and BLT2 in post-PT HAEC HD-N (especially D/T) suggests generalized epithelial barrier derangement with possible etiologic implications for HAEC.</p><p><strong>Level of evidence: </strong>Ⅱ.</p>","PeriodicalId":16733,"journal":{"name":"Journal of pediatric surgery","volume":" ","pages":"161900"},"PeriodicalIF":2.4000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Impact of Epithelial Claudin-4 and Leukotriene B4 Receptor 2 in Normoganglionic Hirschsprung Disease Colon on Post Pull-through Enterocolitis.\",\"authors\":\"Kumpei Abe, Masahiro Takeda, Asuka Ishiyama, Masahiro Shimizu, Hiroki Goto, Hisae Iida, Takashi Fujimoto, Eri Ueda-Abe, Shunsuke Yamada, Kentaro Fujiwara, Soichi Shibuya, Takanori Ochi, Rumi Arii, Yuta Yazaki, Go Miyano, Masahiko Urao, Tadaharu Okazaki, Hiroyuki Koga, Geoffrey J Lane, Atsuyuki Yamataka, Kazuto Suda\",\"doi\":\"10.1016/j.jpedsurg.2024.161900\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>To investigate whether Leukotriene B4 receptor 2 (BLT-2), an upstream regulator of tight junction protein (TJP) Claudin-4, and TJPs could be etiologic factors in Hirschsprung-associated enterocolitis (HAEC) after pull-through (PT) for Hirschsprung disease (HD).</p><p><strong>Methods: </strong>Normoganglionic colon (HD-N) and aganglionic rectum (HD-A) specimens from rectal/rectosigmoid (R/RS) or descending/transverse (D/T) HD were assessed using quantitative polymerase chain reaction (qPCR) for Occludin, TJP-1, TJP-2, Junctional adhesion molecule (JAM)-1, JAM-2, Claudin-1, Claudin-3, Claudin-4, and BLT-2 and immunoblotting for Claudin-4 using fresh specimens obtained intraoperatively (2021-2024; n = 17; R/RS = 15 and D/T = 2). Claudin-4 immunohistochemistry was also evaluated quantitatively using preserved (n = 29; R/RS = 20 and D/T = 9; 2009-2021) and fresh HD specimens for comparison with anorectal malformation patients having colostomy closure as controls (n = 42) and between HD-A versus HD-N, R/RS versus D/T, and HAEC (+) versus HAEC (-). Technically inadequate or transitional zone PT were excluded.</p><p><strong>Results: </strong>Subjects were 123 PT cases. Mean ages at PT/colostomy closure (years) were R/RS: 2.7 ± 2.9, D/T: 1.6 ± 2.2, and controls: 1.4 ± 0.7. Postoperative HAEC occurred 18 times in 14 PT cases (grade I = 5, grade II = 13). Post-PT HAEC was significantly more frequent in D/T (50.0% versus 6.4%; p < 0.001); Claudin-4 was significantly lower in HD-N from post-PT HAEC cases, especially D/T (p < 0.05) on immunohistochemistry. Claudin-4 was significantly lower in HD-N/HD-A compared with controls on immunoblotting (p < 0.05) and immunohistochemistry (p < 0.001). qPCR showed TJP-1, TJP-2, JAM-1, JAM-2, Claudin-4, and BLT-2 were significantly lower in HD-N/HD-A compared with controls.</p><p><strong>Conclusions: </strong>Lower Claudin-4 and BLT2 in post-PT HAEC HD-N (especially D/T) suggests generalized epithelial barrier derangement with possible etiologic implications for HAEC.</p><p><strong>Level of evidence: </strong>Ⅱ.</p>\",\"PeriodicalId\":16733,\"journal\":{\"name\":\"Journal of pediatric surgery\",\"volume\":\" \",\"pages\":\"161900\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of pediatric surgery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jpedsurg.2024.161900\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"PEDIATRICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of pediatric surgery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jpedsurg.2024.161900","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/6 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PEDIATRICS","Score":null,"Total":0}
Impact of Epithelial Claudin-4 and Leukotriene B4 Receptor 2 in Normoganglionic Hirschsprung Disease Colon on Post Pull-through Enterocolitis.
Purpose: To investigate whether Leukotriene B4 receptor 2 (BLT-2), an upstream regulator of tight junction protein (TJP) Claudin-4, and TJPs could be etiologic factors in Hirschsprung-associated enterocolitis (HAEC) after pull-through (PT) for Hirschsprung disease (HD).
Methods: Normoganglionic colon (HD-N) and aganglionic rectum (HD-A) specimens from rectal/rectosigmoid (R/RS) or descending/transverse (D/T) HD were assessed using quantitative polymerase chain reaction (qPCR) for Occludin, TJP-1, TJP-2, Junctional adhesion molecule (JAM)-1, JAM-2, Claudin-1, Claudin-3, Claudin-4, and BLT-2 and immunoblotting for Claudin-4 using fresh specimens obtained intraoperatively (2021-2024; n = 17; R/RS = 15 and D/T = 2). Claudin-4 immunohistochemistry was also evaluated quantitatively using preserved (n = 29; R/RS = 20 and D/T = 9; 2009-2021) and fresh HD specimens for comparison with anorectal malformation patients having colostomy closure as controls (n = 42) and between HD-A versus HD-N, R/RS versus D/T, and HAEC (+) versus HAEC (-). Technically inadequate or transitional zone PT were excluded.
Results: Subjects were 123 PT cases. Mean ages at PT/colostomy closure (years) were R/RS: 2.7 ± 2.9, D/T: 1.6 ± 2.2, and controls: 1.4 ± 0.7. Postoperative HAEC occurred 18 times in 14 PT cases (grade I = 5, grade II = 13). Post-PT HAEC was significantly more frequent in D/T (50.0% versus 6.4%; p < 0.001); Claudin-4 was significantly lower in HD-N from post-PT HAEC cases, especially D/T (p < 0.05) on immunohistochemistry. Claudin-4 was significantly lower in HD-N/HD-A compared with controls on immunoblotting (p < 0.05) and immunohistochemistry (p < 0.001). qPCR showed TJP-1, TJP-2, JAM-1, JAM-2, Claudin-4, and BLT-2 were significantly lower in HD-N/HD-A compared with controls.
Conclusions: Lower Claudin-4 and BLT2 in post-PT HAEC HD-N (especially D/T) suggests generalized epithelial barrier derangement with possible etiologic implications for HAEC.
期刊介绍：
The journal presents original contributions as well as a complete international abstracts section and other special departments to provide the most current source of information and references in pediatric surgery. The journal is based on the need to improve the surgical care of infants and children, not only through advances in physiology, pathology and surgical techniques, but also by attention to the unique emotional and physical needs of the young patient.
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