The Loss of YTHDC1 in Gut Macrophages Exacerbates Inflammatory Bowel Disease
Abstract The nuclear N6‐methyladenosine (m6A) reader YT521‐B homology‐domain‐containing protein 1 (YTHDC1) is required to maintain embryonic stem cell identity. However, little is known about its biological functions in intestinal‐resident macrophages and inflammatory bowel disease (IBD). Herein, it...
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Wiley
2023-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202205620 |
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| author | Xuejun Ge Gang Xue Yan Ding Ran Li Kaining Hu Tengjiao Xu Ming Sun Wang Liao Bin Zhao Chuangyu Wen Jie Du |
| author_facet | Xuejun Ge Gang Xue Yan Ding Ran Li Kaining Hu Tengjiao Xu Ming Sun Wang Liao Bin Zhao Chuangyu Wen Jie Du |
| author_sort | Xuejun Ge |
| collection | DOAJ |
| description | Abstract The nuclear N6‐methyladenosine (m6A) reader YT521‐B homology‐domain‐containing protein 1 (YTHDC1) is required to maintain embryonic stem cell identity. However, little is known about its biological functions in intestinal‐resident macrophages and inflammatory bowel disease (IBD). Herein, it is demonstrated that macrophage‐specific depletion or insufficiency of YTHDC1 accelerates IBD development in animal models. On the molecular basis, YTHDC1 reduction in IBD‐derived macrophages is attributed to Zinc finger protein 36 (ZFP36)‐induced mRNA degradation. Importantly, transcriptome profiling and mechanistic assays unveil that YTHDC1 in macrophages regulates Ras homolog family member H (RHOH) to suppress inflammatory responses and fine‐tunes NME nucleoside diphosphate kinase 1 (NME1) to enhance the integrity of colonic epithelial barrier, respectively. Collectively, this study identifies YTHDC1 as an important factor for the resolution of inflammatory responses and restoration of colonic epithelial barrier in the setting of IBD. |
| format | Article |
| id | doaj-art-58db5e7294c84f2a88a4c20a0b880ba3 |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2023-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-58db5e7294c84f2a88a4c20a0b880ba32025-08-20T03:04:57ZengWileyAdvanced Science2198-38442023-05-011014n/an/a10.1002/advs.202205620The Loss of YTHDC1 in Gut Macrophages Exacerbates Inflammatory Bowel DiseaseXuejun Ge0Gang Xue1Yan Ding2Ran Li3Kaining Hu4Tengjiao Xu5Ming Sun6Wang Liao7Bin Zhao8Chuangyu Wen9Jie Du10Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials Shanxi Medical University School and Hospital of Stomatology Taiyuan Shanxi 030001 ChinaDepartment of Gastroenterology Second Hospital of Shanxi Medical University Taiyuan Shanxi 030001 ChinaDepartment of Dermatology Hainan Provincial Hospital of Skin Disease Haikou Hainan 570000 ChinaShanxi Province Key Laboratory of Oral Diseases Prevention and New Materials Shanxi Medical University School and Hospital of Stomatology Taiyuan Shanxi 030001 ChinaDepartment of Human Genetics The University of Chicago Chicago IL 60637 USADepartment of Dermatology Hainan Medical University Affiliated Dermatology Hospital of Hainan Medical College Haikou Hainan 570000 ChinaCollege of Life Sciences Mudanjiang Medical University Mudanjiang Heilongjiang 157011 ChinaDepartment of Cardiology Hainan General Hospital and Hainan Affiliated Hospital of Hainan Medical University Haikou 570311 ChinaShanxi Province Key Laboratory of Oral Diseases Prevention and New Materials Shanxi Medical University School and Hospital of Stomatology Taiyuan Shanxi 030001 ChinaCentral Laboratory Affiliated Dongguan Hospital Southern Medical University Dongguan Guangdong 523108 ChinaShanxi Province Key Laboratory of Oral Diseases Prevention and New Materials Shanxi Medical University School and Hospital of Stomatology Taiyuan Shanxi 030001 ChinaAbstract The nuclear N6‐methyladenosine (m6A) reader YT521‐B homology‐domain‐containing protein 1 (YTHDC1) is required to maintain embryonic stem cell identity. However, little is known about its biological functions in intestinal‐resident macrophages and inflammatory bowel disease (IBD). Herein, it is demonstrated that macrophage‐specific depletion or insufficiency of YTHDC1 accelerates IBD development in animal models. On the molecular basis, YTHDC1 reduction in IBD‐derived macrophages is attributed to Zinc finger protein 36 (ZFP36)‐induced mRNA degradation. Importantly, transcriptome profiling and mechanistic assays unveil that YTHDC1 in macrophages regulates Ras homolog family member H (RHOH) to suppress inflammatory responses and fine‐tunes NME nucleoside diphosphate kinase 1 (NME1) to enhance the integrity of colonic epithelial barrier, respectively. Collectively, this study identifies YTHDC1 as an important factor for the resolution of inflammatory responses and restoration of colonic epithelial barrier in the setting of IBD.https://doi.org/10.1002/advs.202205620inflammatory bowel diseasemacrophageNme1RhohYTHDC1 |
| spellingShingle | Xuejun Ge Gang Xue Yan Ding Ran Li Kaining Hu Tengjiao Xu Ming Sun Wang Liao Bin Zhao Chuangyu Wen Jie Du The Loss of YTHDC1 in Gut Macrophages Exacerbates Inflammatory Bowel Disease Advanced Science inflammatory bowel disease macrophage Nme1 Rhoh YTHDC1 |
| title | The Loss of YTHDC1 in Gut Macrophages Exacerbates Inflammatory Bowel Disease |
| title_full | The Loss of YTHDC1 in Gut Macrophages Exacerbates Inflammatory Bowel Disease |
| title_fullStr | The Loss of YTHDC1 in Gut Macrophages Exacerbates Inflammatory Bowel Disease |
| title_full_unstemmed | The Loss of YTHDC1 in Gut Macrophages Exacerbates Inflammatory Bowel Disease |
| title_short | The Loss of YTHDC1 in Gut Macrophages Exacerbates Inflammatory Bowel Disease |
| title_sort | loss of ythdc1 in gut macrophages exacerbates inflammatory bowel disease |
| topic | inflammatory bowel disease macrophage Nme1 Rhoh YTHDC1 |
| url | https://doi.org/10.1002/advs.202205620 |
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