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Research Article
Xiaoming Zhang
Zhejiang University School of Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0003-2292-4485
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Recently, gut microbiota for various pathogens has attracted attention. The present study investigated the role of gut microbiota unmethylated cytosine phosphate guanine DNA (CpG-DNA) on liver Kupffer cells (KCs) inflammatory cytokine interleukin-1β (IL-1β) in diabetic rats. We induced diabetic rats models and sequenced the gut microbiota composition of fecal samples. We also applied CpG-DNA and TLR9 inhibitor on KCs to investigate the regulation of inflammatory cytokine IL-1β and Toll-like receptor 9 (TLR9) signaling pathway. We found a significant difference of gut microbiota between the control and the diabetic rats with increased Clostridium. Meanwhile, diabetes could upregulate TLR9 in KCs and increase IL-1β concentration. Furthermore, high concentration of unmethylated CpG-DNA could significantly increase IL-1β secretion while it was suppressed by TLR9 inhibitor in KCs cultured in high glucose medium. Our study suggests that unmethylated CpG-DNA, which was highly expressed in diabetic rats, activated KCs through TLR9, and induced IL-1β secretion in vitro and in vivo which plays an important role in diabetic liver inflammation. It may contribute to the progress of the diabetes.
Keywords
Diabetes mellitus, Gut microbiota, unmethylated CpG-DNA, KCs, Inflammation
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This preprint is under consideration at Molecular and Cellular Biochemistry. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Xiaoming Zhang
Zhejiang University School of Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0003-2292-4485
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 12 Mar, 2021
No community comments so far
Review #? received
Received 07 Mar, 2021
Reviewers invited
Invitations sent on 04 Mar, 2021
Editor assigned
On 01 Mar, 2021
First submitted
On 25 Feb, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Applied Biochemistry
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Recently, gut microbiota for various pathogens has attracted attention. The present study investigated the role of gut microbiota unmethylated cytosine phosphate guanine DNA (CpG-DNA) on liver Kupffer cells (KCs) inflammatory cytokine interleukin-1β (IL-1β) in diabetic rats. We induced diabetic rats models and sequenced the gut microbiota composition of fecal samples. We also applied CpG-DNA and TLR9 inhibitor on KCs to investigate the regulation of inflammatory cytokine IL-1β and Toll-like receptor 9 (TLR9) signaling pathway. We found a significant difference of gut microbiota between the control and the diabetic rats with increased Clostridium. Meanwhile, diabetes could upregulate TLR9 in KCs and increase IL-1β concentration. Furthermore, high concentration of unmethylated CpG-DNA could significantly increase IL-1β secretion while it was suppressed by TLR9 inhibitor in KCs cultured in high glucose medium. Our study suggests that unmethylated CpG-DNA, which was highly expressed in diabetic rats, activated KCs through TLR9, and induced IL-1β secretion in vitro and in vivo which plays an important role in diabetic liver inflammation. It may contribute to the progress of the diabetes.
Figure 1
Figure 2
Figure 3
Figure 4
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