Transcriptomic analysis reveals the regulatory mechanism underlying the indirubin-mediated amelioration of dextran sulfate sodium-induced colitis in mice
AbstractContext Aryl hydrocarbon receptor (AhR) agonists are potential therapeutic agents for ulcerative colitis (UC). Indirubin (IDR), which is a natural AhR ligand approved for leukemia treatment, ameliorates dextran sulfate sodium (DSS)-induced colitis in mice. However, the therapeutic mechanisms...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Pharmaceutical Biology |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/13880209.2023.2233565 |
| _version_ | 1827302085338595328 |
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| author | Zhe Liu Jin-ru Zhang Yong-xiang Huang Xue-ying Li Hai-peng Zhu Rui-yi Yang Song Chen |
| author_facet | Zhe Liu Jin-ru Zhang Yong-xiang Huang Xue-ying Li Hai-peng Zhu Rui-yi Yang Song Chen |
| author_sort | Zhe Liu |
| collection | DOAJ |
| description | AbstractContext Aryl hydrocarbon receptor (AhR) agonists are potential therapeutic agents for ulcerative colitis (UC). Indirubin (IDR), which is a natural AhR ligand approved for leukemia treatment, ameliorates dextran sulfate sodium (DSS)-induced colitis in mice. However, the therapeutic mechanisms of IDR are unknown, limiting its application.Objective This study explores the therapeutic mechanisms of IDR in DSS-induced colitis using transcriptomic analysis.Materials and methods Male BALB/c mice were categorized to six groups: normal, DSS model (2% DSS), IDR treatment (10, 20 and 40 mg/kg), and sulfasalazine (520 mg/kg) groups. The drugs were intragastrically administered for 7 consecutive days. The disease activity index (DAI) was recorded. After euthanasia, the colon length was measured, and histopathological examination, immunohistochemistry staining using F4/80, and colonic transcriptomic analysis were conducted. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB) were conducted to verify our findings.Results Compared with DSS, IDR treatment decreased the DAI score by 64.9% and increased colon length by 26.2%. Moreover, it alleviated mucosal injury and reduced macrophage infiltration. Transcriptomic analysis identified several downregulated genes (Igkvs and Nlrp3), as well as Nlrp3/Il1β and hemoglobin gene networks, after IDR treatment. The abundances of NF-κB p65, NLRP3, IL-1β, and HBA decreased by 69.1, 59.4, 81.1, and 83.0% respectively, after IDR treatment.Discussion and conclusion Apart from the well-documented NF-κB signalling pathway, IL-17A, and NLRP3-IL-1β, the suppression of haemoglobin-induced lipid peroxidation could be a previously unknown mechanism of IDR. Our study can help improve its application for UC treatment. |
| first_indexed | 2024-03-09T00:09:15Z |
| format | Article |
| id | doaj.art-7959cf9810e34004b272385162b47c29 |
| institution | Directory Open Access Journal |
| issn | 1388-0209 1744-5116 |
| language | English |
| last_indexed | 2024-04-24T16:38:24Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj.art-7959cf9810e34004b272385162b47c292024-03-29T11:10:26ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162023-12-016111082109310.1080/13880209.2023.2233565Transcriptomic analysis reveals the regulatory mechanism underlying the indirubin-mediated amelioration of dextran sulfate sodium-induced colitis in miceZhe Liu0Jin-ru Zhang1Yong-xiang Huang2Xue-ying Li3Hai-peng Zhu4Rui-yi Yang5Song Chen6Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, P.R. ChinaScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, P.R. ChinaScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, P.R. ChinaScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, P.R. ChinaDongguan Ninth People’s hospital, Dongguan, P.R. ChinaScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, P.R. ChinaScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, P.R. ChinaAbstractContext Aryl hydrocarbon receptor (AhR) agonists are potential therapeutic agents for ulcerative colitis (UC). Indirubin (IDR), which is a natural AhR ligand approved for leukemia treatment, ameliorates dextran sulfate sodium (DSS)-induced colitis in mice. However, the therapeutic mechanisms of IDR are unknown, limiting its application.Objective This study explores the therapeutic mechanisms of IDR in DSS-induced colitis using transcriptomic analysis.Materials and methods Male BALB/c mice were categorized to six groups: normal, DSS model (2% DSS), IDR treatment (10, 20 and 40 mg/kg), and sulfasalazine (520 mg/kg) groups. The drugs were intragastrically administered for 7 consecutive days. The disease activity index (DAI) was recorded. After euthanasia, the colon length was measured, and histopathological examination, immunohistochemistry staining using F4/80, and colonic transcriptomic analysis were conducted. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB) were conducted to verify our findings.Results Compared with DSS, IDR treatment decreased the DAI score by 64.9% and increased colon length by 26.2%. Moreover, it alleviated mucosal injury and reduced macrophage infiltration. Transcriptomic analysis identified several downregulated genes (Igkvs and Nlrp3), as well as Nlrp3/Il1β and hemoglobin gene networks, after IDR treatment. The abundances of NF-κB p65, NLRP3, IL-1β, and HBA decreased by 69.1, 59.4, 81.1, and 83.0% respectively, after IDR treatment.Discussion and conclusion Apart from the well-documented NF-κB signalling pathway, IL-17A, and NLRP3-IL-1β, the suppression of haemoglobin-induced lipid peroxidation could be a previously unknown mechanism of IDR. Our study can help improve its application for UC treatment.https://www.tandfonline.com/doi/10.1080/13880209.2023.2233565Aryl hydrocarbon receptor (AhR)hemoglobin (Hb)interleukin-17A (IL-17A)NLR family pyrin domain containing 3 (NLRP3)nuclear factor-kappa B (NF-κB) |
| spellingShingle | Zhe Liu Jin-ru Zhang Yong-xiang Huang Xue-ying Li Hai-peng Zhu Rui-yi Yang Song Chen Transcriptomic analysis reveals the regulatory mechanism underlying the indirubin-mediated amelioration of dextran sulfate sodium-induced colitis in mice Pharmaceutical Biology Aryl hydrocarbon receptor (AhR) hemoglobin (Hb) interleukin-17A (IL-17A) NLR family pyrin domain containing 3 (NLRP3) nuclear factor-kappa B (NF-κB) |
| title | Transcriptomic analysis reveals the regulatory mechanism underlying the indirubin-mediated amelioration of dextran sulfate sodium-induced colitis in mice |
| title_full | Transcriptomic analysis reveals the regulatory mechanism underlying the indirubin-mediated amelioration of dextran sulfate sodium-induced colitis in mice |
| title_fullStr | Transcriptomic analysis reveals the regulatory mechanism underlying the indirubin-mediated amelioration of dextran sulfate sodium-induced colitis in mice |
| title_full_unstemmed | Transcriptomic analysis reveals the regulatory mechanism underlying the indirubin-mediated amelioration of dextran sulfate sodium-induced colitis in mice |
| title_short | Transcriptomic analysis reveals the regulatory mechanism underlying the indirubin-mediated amelioration of dextran sulfate sodium-induced colitis in mice |
| title_sort | transcriptomic analysis reveals the regulatory mechanism underlying the indirubin mediated amelioration of dextran sulfate sodium induced colitis in mice |
| topic | Aryl hydrocarbon receptor (AhR) hemoglobin (Hb) interleukin-17A (IL-17A) NLR family pyrin domain containing 3 (NLRP3) nuclear factor-kappa B (NF-κB) |
| url | https://www.tandfonline.com/doi/10.1080/13880209.2023.2233565 |
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