دورية أكاديمية
ARF1 maintains intestinal homeostasis by modulating gut microbiota and stem cell function.
| العنوان: | ARF1 maintains intestinal homeostasis by modulating gut microbiota and stem cell function. |
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| المؤلفون: | Yu D; China State Key Laboratory of Genetic Engineering, School of Life Sciences, Institute of Developmental Biology and Molecular Medicine, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Children's Hospital, Department of Liver Surgery and Transplantation of Liver Cancer Institute at Zhongshan Hospital, Fudan University, Shanghai 200438, China., Dai Q; China State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China., Wang Z; China State Key Laboratory of Genetic Engineering, School of Life Sciences, Institute of Developmental Biology and Molecular Medicine, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Children's Hospital, Department of Liver Surgery and Transplantation of Liver Cancer Institute at Zhongshan Hospital, Fudan University, Shanghai 200438, China., Hou SX; China State Key Laboratory of Genetic Engineering, School of Life Sciences, Institute of Developmental Biology and Molecular Medicine, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Children's Hospital, Department of Liver Surgery and Transplantation of Liver Cancer Institute at Zhongshan Hospital, Fudan University, Shanghai 200438, China. Electronic address: stevenhou@fudan.edu.cn., Sun LV; China State Key Laboratory of Genetic Engineering, School of Life Sciences, Institute of Developmental Biology and Molecular Medicine, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Children's Hospital, Department of Liver Surgery and Transplantation of Liver Cancer Institute at Zhongshan Hospital, Fudan University, Shanghai 200438, China. Electronic address: lingsun@fudan.edu.cn. |
| المصدر: | Life sciences [Life Sci] 2023 Sep 01; Vol. 328, pp. 121902. Date of Electronic Publication: 2023 Jun 29. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0375521 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0631 (Electronic) Linking ISSN: 00243205 NLM ISO Abbreviation: Life Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2008->: Amsterdam : Elsevier Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press. |
| مواضيع طبية MeSH: | Intestine, Small*/cytology , Intestine, Small*/metabolism , Intestine, Small*/microbiology , ADP-Ribosylation Factor 1*/metabolism , Gastrointestinal Microbiome* , Adult Stem Cells*/metabolism, Animals ; Mice ; Mice, Knockout ; Dysbiosis/metabolism ; Anti-Bacterial Agents/administration & dosage ; Transcription, Genetic ; Homeostasis ; Metabolic Networks and Pathways |
| مستخلص: | Aims: The small GTPase protein ARF1 has been shown to be involved in the lipolysis pathway and to selectively kill stem cells in Drosophila melanogaster. However, the role of ARF1 in mammalian intestinal homeostasis remains elusive. This study aimed to explore the role of ARF1 in intestinal epithelial cells (IECs) and reveal the possible mechanism. Materials and Methods: IEC-specific ARF1 deletion mouse model was used to evaluate the role of ARF1 in intestine. Immunohistochemistry and immunofluorescence analyses were performed to detect specific cell type markers, and intestinal organoids were cultured to assess intestinal stem cell (ISC) proliferation and differentiation. Fluorescence in situ hybridization, 16S rRNA-seq analysis, and antibiotic treatments were conducted to elucidate the role of gut microbes in ARF1-mediated intestinal function and the underlying mechanism. Colitis was induced in control and ARF1-deficient mice by dextran sulfate sodium (DSS). RNA-seq was performed to elucidate the transcriptomic changes after ARF1 deletion. Key Findings: ARF1 was essential for ISC proliferation and differentiation. Loss of ARF1 increased susceptibility to DSS-induced colitis and gut microbial dysbiosis. Gut microbiota depletion by antibiotics could rescue the intestinal abnormalities to a certain extent. Furthermore, RNA-seq analysis revealed alterations in multiple metabolic pathways. Significance: This work is the first to elucidate the essential role of ARF1 in regulating gut homeostasis, and provides novel insights into the pathogenesis of intestinal diseases and potential therapeutic targets. Competing Interests: Declaration of competing interest All authors declare that they have no competing interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023. Published by Elsevier Inc.) |
| فهرسة مساهمة: | Keywords: ARF1; Colitis; Gut microbiota; Intestinal homeostasis; Intestinal stem cell |
| المشرفين على المادة: | EC 3.6.5.2 (ADP-Ribosylation Factor 1) 0 (Anti-Bacterial Agents) |
| تواريخ الأحداث: | Date Created: 20230701 Date Completed: 20230725 Latest Revision: 20230725 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.lfs.2023.121902 |
| PMID: | 37392777 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-0631 |
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| DOI: | 10.1016/j.lfs.2023.121902 |