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Exosome‐like nanoparticles from Mulberry bark prevent DSS‐induced colitis via the AhR/COPS8 pathway

EMBO reports, 2022-02, Vol.23 (3), p.e53365-n/a [Peer Reviewed Journal]

2022 The Authors ;2022 The Authors. ;2022 EMBO ;ISSN: 1469-221X ;EISSN: 1469-3178 ;DOI: 10.15252/embr.202153365 ;PMID: 34994476

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Title:
Exosome‐like nanoparticles from Mulberry bark prevent DSS‐induced colitis via the AhR/COPS8 pathway
Author: Sriwastva, Mukesh K ; Deng, Zhong‐Bin ; Wang, Bomei ; Teng, Yun ; Kumar, Anil ; Sundaram, Kumaran ; Mu, Jingyao ; Lei, Chao ; Dryden, Gerald W ; Xu, Fangyi ; Zhang, Lifeng ; Yan, Jun ; Zhang, Xiang ; Park, Juw Won ; Merchant, Michael L ; Egilmez, Nejat K ; Zhang, Huang‐Ge
Subjects: AhR ; Animals ; anti‐microbial peptides ; Arrays ; Bark ; Colitis ; Colitis - chemically induced ; Colitis - metabolism ; Colitis - prevention & control ; COP9/COPS8 ; Digestive system ; Digestive tract ; Disease Models, Animal ; Downstream effects ; Epithelial cells ; Epithelium ; Exosomes - metabolism ; heat shock protein family A (Hsp70) member 8 ; Heat shock proteins ; Homeostasis ; Homology ; Hsp70 protein ; inflammation ; Inflammatory bowel disease ; Inflammatory diseases ; Intestinal microflora ; Intestine ; Mice ; Mice, Inbred C57BL ; Microbiomes ; Microbiota ; Microorganisms ; Morus ; Mulberry bark derived exosome‐like nanoparticles ; Nanoparticles ; Pathways ; Peptides ; Plant Bark - metabolism ; Signal transduction ; Signaling
Is Part Of: EMBO reports, 2022-02, Vol.23 (3), p.e53365-n/a
Description: Bark protects the tree against environmental insults. Here, we analyzed whether this defensive strategy could be utilized to broadly enhance protection against colitis. As a proof of concept, we show that exosome‐like nanoparticles (MBELNs) derived from edible mulberry bark confer protection against colitis in a mouse model by promoting heat shock protein family A (Hsp70) member 8 (HSPA8)‐mediated activation of the AhR signaling pathway. Activation of this pathway in intestinal epithelial cells leads to the induction of COP9 Constitutive Photomorphogenic Homolog Subunit 8 (COPS8). Utilizing a gut epithelium‐specific knockout of COPS8, we demonstrate that COPS8 acts downstream of the AhR pathway and is required for the protective effect of MBELNs by inducing an array of anti‐microbial peptides. Our results indicate that MBELNs represent an undescribed mode of inter‐kingdom communication in the mammalian intestine through an AhR‐COPS8‐mediated anti‐inflammatory pathway. These data suggest that inflammatory pathways in a microbiota‐enriched intestinal environment are regulated by COPS8 and that edible plant‐derived ELNs may hold the potential as new agents for the prevention and treatment of gut‐related inflammatory disease. Synopsis Mulberry bark derived exosome‐like nanoparticles (MBELNs) prevent gut inflammation via plant heat shock protein HSPA8‐mediated activation of AhR/COPS8 pathways. Treatment with MBELNs promotes the restoration of gut microbiome homeostasis, ameliorating intestinal inflammatory pathologies. Mulberry bark derived exosome‐like nanoparticles (MBELNs) prevent mouse colitis via the AhR/COPS8 pathway. Binding of MBELN‐derived heat shock protein HSPA8 to AhR leads to the activation of AhR signaling. Activation of AhR leads to the induction of an array of anti‐microbial peptides (AMPs) via COP9/COPS8. AhR/COPS8‐dependent induction of AMPs inhibits intestinal inflammation and alters fecal gut microbiota composition. Mulberry bark derived exosome‐like nanoparticles (MBELNs) prevent gut inflammation via plant heat shock protein HSPA8‐mediated activation of AhR/COPS8 pathways. Treatment with MBELNs promotes the restoration of gut microbiome homeostasis, ameliorating intestinal inflammatory pathologies.
Publisher: England: Blackwell Publishing Ltd
Language: English
Identifier: ISSN: 1469-221X
EISSN: 1469-3178
DOI: 10.15252/embr.202153365
PMID: 34994476
Source: Geneva Foundation Free Medical Journals at publisher websites
MEDLINE
PubMed Central

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Exosome‐like nanoparticles from Mulberry bark prevent DSS‐induced colitis via the AhR/COPS8 pathway

2022 The Authors ;2022 The Authors. ;2022 EMBO ;ISSN: 1469-221X ;EISSN: 1469-3178 ;DOI: 10.15252/embr.202153365 ;PMID: 34994476

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