دورية أكاديمية
Identification of a functional peptide of a probiotic bacterium-derived protein for the sustained effect on preventing colitis.
العنوان: | Identification of a functional peptide of a probiotic bacterium-derived protein for the sustained effect on preventing colitis. |
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المؤلفون: | Kaur H; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA., Ali SA; Division of Proteomics of Stem Cell and Cancer, German Cancer Research Center, Heidelberg, Germany., Short SP; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Williams CS; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Goettel JA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA., Washington MK; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Peek RM Jr; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Acra SA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA., Yan F; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA. |
المصدر: | Gut microbes [Gut Microbes] 2023 Dec; Vol. 15 (2), pp. 2264456. Date of Electronic Publication: 2023 Oct 10. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101495343 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1949-0984 (Electronic) Linking ISSN: 19490976 NLM ISO Abbreviation: Gut Microbes Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2015- : Philadelphia, PA : Taylor & Francis Original Publication: Austin, Tex. : Landes Bioscience |
مواضيع طبية MeSH: | Gastrointestinal Microbiome* , Colitis*/prevention & control , Probiotics*/pharmacology, Adult ; Humans ; Animals ; Mice ; Bacterial Proteins/genetics ; Peptides |
مستخلص: | Several probiotic-derived factors have been identified as effectors of probiotics for exerting beneficial effects on the host. However, there is a paucity of studies to elucidate mechanisms of their functions. p40, a secretory protein, is originally isolated from a probiotic bacterium, Lactobacillus rhamnosus GG. Thus, this study aimed to apply structure-functional analysis to define the functional peptide of p40 that modulates the epigenetic program in intestinal epithelial cells for sustained prevention of colitis. In silico analysis revealed that p40 is composed of a signal peptide (1-28 residues) followed by a coiled-coil domain with uncharacterized function on the N-terminus, a linker region, and a β-sheet domain with high homology to CHAP on the C-terminus. Based on the p40 three-dimensional structure model, two recombinant p40 peptides were generated, p40N120 (28-120 residues) and p40N180 (28-180 residues) that contain first two and first three coiled coils, respectively. Compared to full-length p40 (p40F) and p40N180, p40N120 showed similar or higher effects on up-regulating expression of Setd1b (encoding a methyltransferase), promoting mono- and trimethylation of histone 3 on lysine 4 (H3K4me1/3), and enhancing Tgfb gene expression and protein production that leads to SMAD2 phosphorylation in human colonoids and a mouse colonic epithelial cell line. Furthermore, supplementation with p40F and p40N120 in early life increased H3K4me1, Tgfb expression and differentiation of regulatory T cells (Tregs) in the colon, and mitigated disruption of epithelial barrier and inflammation induced by DSS in adult mice. This study reveals the structural feature of p40 and identifies a functional peptide of p40 that could maintain intestinal homeostasis. |
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معلومات مُعتمدة: | R01 DK081134 United States DK NIDDK NIH HHS; R01 CA077955 United States CA NCI NIH HHS; K01 DK123495 United States DK NIDDK NIH HHS; P30 DK058404 United States DK NIDDK NIH HHS; RC2 DK118640 United States DK NIDDK NIH HHS; P01 CA116087 United States CA NCI NIH HHS; R03 DK123489 United States DK NIDDK NIH HHS; R01 DK058587 United States DK NIDDK NIH HHS |
فهرسة مساهمة: | Keywords: Histone methyltransferase; Setd1β; TGFβ; intestinal epithelial cell; p40 |
المشرفين على المادة: | 0 (Bacterial Proteins) 0 (Peptides) |
تواريخ الأحداث: | Date Created: 20231010 Date Completed: 20231011 Latest Revision: 20240210 |
رمز التحديث: | 20240210 |
مُعرف محوري في PubMed: | PMC10566403 |
DOI: | 10.1080/19490976.2023.2264456 |
PMID: | 37815528 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1949-0984 |
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DOI: | 10.1080/19490976.2023.2264456 |