Dihydroartemisinin Modulates Enteric Glial Cell Heterogeneity to Alleviate Colitis

Abstract The precise mechanism underlying the therapeutic effects of dihydroartemisinin (DHA) in alleviating colitis remains incompletely understood. A strong correlation existed between the elevation of glial fibrillary acidic protein (GFAP)+/S100 calcium binding protein B (S100β)+ enteric glial ce...

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Main Authors: Peishan Qiu, Ying Chang, Xiaoyu Chen, Shaoqi Wang, Haihang Nie, Yuntian Hong, Meng Zhang, Haizhou Wang, Cong Xiao, Yuhua Chen, Lan Liu, Qiu Zhao
Format: Article
Language:English
Published: Wiley 2024-09-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202403461
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author Peishan Qiu
Ying Chang
Xiaoyu Chen
Shaoqi Wang
Haihang Nie
Yuntian Hong
Meng Zhang
Haizhou Wang
Cong Xiao
Yuhua Chen
Lan Liu
Qiu Zhao
author_facet Peishan Qiu
Ying Chang
Xiaoyu Chen
Shaoqi Wang
Haihang Nie
Yuntian Hong
Meng Zhang
Haizhou Wang
Cong Xiao
Yuhua Chen
Lan Liu
Qiu Zhao
author_sort Peishan Qiu
collection DOAJ
description Abstract The precise mechanism underlying the therapeutic effects of dihydroartemisinin (DHA) in alleviating colitis remains incompletely understood. A strong correlation existed between the elevation of glial fibrillary acidic protein (GFAP)+/S100 calcium binding protein B (S100β)+ enteric glial cells (EGCs) in inflamed colonic tissues and the disruption of the intestinal epithelial barrier (IEB) and gut vascular barrier (GVB) observed in chronic colitis. DHA demonstrated efficacy in restoring the functionality of the dual gut barrier while concurrently attenuating intestinal inflammation. Mechanistically, DHA inhibited the transformation of GFAP+ EGCs into GFAP+/S100β+ EGCs while promoting the differentiation of GFAP+/S100β+ EGCs back into GFAP+ EGCs. Furthermore, DHA induced apoptosis in GFAP+/S100β+ EGCs by inducing cell cycle arrest at the G0/G1 phase. The initial mechanism is further validated that DHA regulates EGC heterogeneity by improving dysbiosis in colitis. These findings underscore the multifaceted therapeutic potential of DHA in ameliorating colitis by improving dysbiosis, modulating EGC heterogeneity, and preserving gut barrier integrity, thus offering promising avenues for novel therapeutic strategies for inflammatory bowel diseases.
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spelling doaj-art-adcdae1f83494a27a489a2a6dd46b4622025-08-20T01:55:16ZengWileyAdvanced Science2198-38442024-09-011135n/an/a10.1002/advs.202403461Dihydroartemisinin Modulates Enteric Glial Cell Heterogeneity to Alleviate ColitisPeishan Qiu0Ying Chang1Xiaoyu Chen2Shaoqi Wang3Haihang Nie4Yuntian Hong5Meng Zhang6Haizhou Wang7Cong Xiao8Yuhua Chen9Lan Liu10Qiu Zhao11Department of Gastroenterology Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaDepartment of Gastroenterology Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaDepartment of Gastroenterology Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaDepartment of Gastroenterology Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaDepartment of Gastroenterology Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaDepartment of Gastroenterology Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaDepartment of Gastroenterology Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaDepartment of Gastroenterology Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaDepartment of Gastroenterology Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaDepartment of Gastroenterology Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaDepartment of Gastroenterology Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaDepartment of Gastroenterology Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaAbstract The precise mechanism underlying the therapeutic effects of dihydroartemisinin (DHA) in alleviating colitis remains incompletely understood. A strong correlation existed between the elevation of glial fibrillary acidic protein (GFAP)+/S100 calcium binding protein B (S100β)+ enteric glial cells (EGCs) in inflamed colonic tissues and the disruption of the intestinal epithelial barrier (IEB) and gut vascular barrier (GVB) observed in chronic colitis. DHA demonstrated efficacy in restoring the functionality of the dual gut barrier while concurrently attenuating intestinal inflammation. Mechanistically, DHA inhibited the transformation of GFAP+ EGCs into GFAP+/S100β+ EGCs while promoting the differentiation of GFAP+/S100β+ EGCs back into GFAP+ EGCs. Furthermore, DHA induced apoptosis in GFAP+/S100β+ EGCs by inducing cell cycle arrest at the G0/G1 phase. The initial mechanism is further validated that DHA regulates EGC heterogeneity by improving dysbiosis in colitis. These findings underscore the multifaceted therapeutic potential of DHA in ameliorating colitis by improving dysbiosis, modulating EGC heterogeneity, and preserving gut barrier integrity, thus offering promising avenues for novel therapeutic strategies for inflammatory bowel diseases.https://doi.org/10.1002/advs.202403461colitisdihydroartemisinindysbiosisenteric glial cellsgut barrierphenotypic transformation
spellingShingle Peishan Qiu
Ying Chang
Xiaoyu Chen
Shaoqi Wang
Haihang Nie
Yuntian Hong
Meng Zhang
Haizhou Wang
Cong Xiao
Yuhua Chen
Lan Liu
Qiu Zhao
Dihydroartemisinin Modulates Enteric Glial Cell Heterogeneity to Alleviate Colitis
Advanced Science
colitis
dihydroartemisinin
dysbiosis
enteric glial cells
gut barrier
phenotypic transformation
title Dihydroartemisinin Modulates Enteric Glial Cell Heterogeneity to Alleviate Colitis
title_full Dihydroartemisinin Modulates Enteric Glial Cell Heterogeneity to Alleviate Colitis
title_fullStr Dihydroartemisinin Modulates Enteric Glial Cell Heterogeneity to Alleviate Colitis
title_full_unstemmed Dihydroartemisinin Modulates Enteric Glial Cell Heterogeneity to Alleviate Colitis
title_short Dihydroartemisinin Modulates Enteric Glial Cell Heterogeneity to Alleviate Colitis
title_sort dihydroartemisinin modulates enteric glial cell heterogeneity to alleviate colitis
topic colitis
dihydroartemisinin
dysbiosis
enteric glial cells
gut barrier
phenotypic transformation
url https://doi.org/10.1002/advs.202403461
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