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Mechanism of bone marrow mesenchymal stem cells secreting miR-26a exosomes affecting high glucose-induced skin fibroblasts function by regulating TLR4/NF-κB signaling

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Abstract

Objective

The aim of this study was to investigate the molecular mechanism of human bone marrow mesenchymal stem cells (hMSCs) secreting miR-26a exosomes on the function of skin fibroblasts.

Methods

Exosomes from hMSCs were extracted and identified by transmission electron microscopy, particle size was analyzed and protein markers were detected. Then, the exosomes were co-cultured with human skin fibroblasts (BJ). CCK-8, Annexin V/P and Transwell assays were used to detect the proliferation, apoptosis, and migration of BJ cells. In addition, the expressions of miR-26a, related proteins, and related inflammatory factors were detected by qRT-PCR, western blotting, and ELISA.

Results

Compared with the high glucose group, the proliferation rate, migration rate, and the expression of α-SMA, bcl-2, TLR4, NF-κB, TNF-α, IL-6, IL- and IL-1 were significantly decreased in the high glucose + MSC-Exo-miR-26a mimics group, while the apoptosis rate and the expression of miR-26a, cleaved-caspase 3, cleaved-caspase 9 and Bax were significantly increased. The results of the high glucose + MSC-Exo-miR-26a inhibitor group were the opposite.

Conclusion

These results suggest that hMSCs cells secreting miR-26a exosomes inhibited the proliferation, migration, and transdifferentiation of high glucose-induced BJ cells, and promoted cell apoptosis, which may be related to the TLR4/NF-κB signaling pathway.

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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by the National Natural Science Foundation of China (No. 81602742).

Author information

Authors and Affiliations

  1. Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, Hubei, China

    Qian Li

  2. Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, Hubei, China

    Ping Huang & Weimin Chen

  3. Division of Periodontology, Diagnostic Sciences, and Dental Hygiene, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA

    Jiarui Bi

Authors
  1. Qian Li
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  2. Ping Huang
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  4. Jiarui Bi
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Contributions

QL and PH performed the research; PH designed the research study; WC contributed essential reagents or tools; WC and JB analyzed the data; QL wrote the paper; All authors approved the final version of the paper.

Corresponding author

Correspondence to Ping Huang.

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Conflict of interest

There is no competing interest.

Ethics approval

The study protocol was approved by the Ethics Committee of Tongji Hospital.

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Responsible Editor: John Di Battista.

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Li, Q., Huang, P., Chen, W. et al. Mechanism of bone marrow mesenchymal stem cells secreting miR-26a exosomes affecting high glucose-induced skin fibroblasts function by regulating TLR4/NF-κB signaling. Inflamm. Res. 70, 811–821 (2021). https://doi.org/10.1007/s00011-021-01478-7

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  • DOI: https://doi.org/10.1007/s00011-021-01478-7

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