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Effects of anti-CD20 monoclonal antibody and IL-10 on pancreatic β cell regeneration in nonobese diabetic mice

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Abstract

Objective

To investigate the effects of anti-CD20 monoclonal antibody (mAb) combined with IL-10 mediated by adenovirus on the regeneration of pancreatic β cells in nonobese diabetic (NOD) mice.

Methods

Serum IL-10, TGF-β, TNF-α, IFN-γ, C-peptide, and insulin were determined using commercial ELISA. Western blot assay and real-time PCR were performed to determine the expression of mRNA and protein expression, respectively. Besides, immunohistochemistry and immunofluorescence were performed.

Results

Immunohistochemisty assay indicated Ngn3 expression showed decrease in the anti-CD20+IL-10 group compared with the other groups (p < 0.05). Immunofluorescence assay showed Pdx-1 and insulin coexpressing cells showed increase in the anti-CD20+IL-10 group. Real-time PCR indicated that the expression of Pdx-1, Pax4, Nkx6.1, and Mafa mRNA showed significant increase in the anti-CD20+IL-10 group compared with the other groups (p < 0.05). The expression of Pdx-1, Pax4, Nkx6.1, and Mafa protein was significantly upregulated in the anti-CD20+IL-10 group compared with that of the other groups (p < 0.05).

Conclusions

Anti-CD20 combined with IL-10 promoted insulin secretion in NOD mice and the controlling of blood glucose. Besides, the combination induced the decrease of TNF-α and IFN-γ, and the elevation of TGF-β. Besides, it may activate the Pdx-1-Ngn3-Pax4-Nkx2.2-Nkx6.1 signaling pathway, and trigger the regeneration of pancreatic β cells.

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Authors and Affiliations

  1. Neuroendocrinological Paediatrics, Affiliated Hospital of Qingdao University, Qingdao, 266003, China

    Fei Tian, Ying Zhang, Jian Jiang, Zhihong Chen & Lijuan Zhang

  2. Endocrinological Paediatrics, Qingdao Women and Children’s Hospital, No. 6, Tongfu Road, Qingdao, 266003, China

    Cheng Li & Tang Li

Authors
  1. Fei Tian
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  2. Cheng Li
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  3. Ying Zhang
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  4. Jian Jiang
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  5. Zhihong Chen
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  6. Lijuan Zhang
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  7. Tang Li
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Contributions

TF drafted the article or revised it critically for important intellectual content; LT finally approved the version to be published; LC, ZY, JJ, CZH, and ZLJ contributed to the conception and design or acquisition of data or analysis and interpretation of data.

Corresponding author

Correspondence to Tang Li.

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The authors declare that they have no conflict of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Ethical considerations

The study protocols were approved by the EC of Qingdao Women and Children Hospital.

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Cite this article

Tian, F., Li, C., Zhang, Y. et al. Effects of anti-CD20 monoclonal antibody and IL-10 on pancreatic β cell regeneration in nonobese diabetic mice. Int J Diabetes Dev Ctries 41, 593–599 (2021). https://doi.org/10.1007/s13410-020-00899-0

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  • DOI: https://doi.org/10.1007/s13410-020-00899-0

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