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Adipose mesenchymal stem cell-derived exosomes accelerate skin wound healing via the lncRNA H19/miR-19b/SOX9 axis

Abstract

It has been reported that adipose mesenchymal stem cells (ADSCs) accelerate wound healing. Moreover, exosomes, which serve as paracrine factors, play a vital role in wound healing. However, the mechanism remains unclear. This research aimed to determine the roles of exosomes derived from ADSCs (ADSC-Exos) in wound skin tissue repair. Flow cytometry and electron microscopy were carried out to identify ADSCs and ADSC-Exos, respectively; RT-qPCR was performed to assess the lncRNA H19 (H19), microRNA19b (miR-19b) and SRY-related high-mobility-group box 9 (SOX9) levels; Western blotting was carried out to evaluate collagen and β-catenin expression; CCK-8, scratch and transwell assays were conducted to evaluate human skin fibroblast (HSF) cell proliferation, migration and invasion, respectively; the potential binding sites between H19 and miR-19b, miR-19b and SOX9 were detected by dual-luciferase reporter gene assay and RIP assay; and H&E staining was conducted to observe skin wound tissues. ADSC-Exos accelerated the proliferation, migration and invasion of HSF cells via H19. H19 acts as a molecular sponge towards miR-19b, which targets SOX9. ADSC-Exos inhibited miR-19b expression via H19, resulting in accelerated HSF proliferation, migration and invasion. ADSC-Exos upregulated SOX9 to activate the Wnt/β-catenin pathway, resulting in accelerated HSF cell proliferation, migration and invasion, and ADSC-Exos promoted skin wound healing via H19 in mice.

The high expression of H19 in ADSC-Exos may upregulate SOX9 expression via miR-19b to accelerate wound healing of skin tissues. Our study may provide novel perspectives for therapy to accelerate skin wound healing.

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Fig. 1: Isolation and identification of ADSCs and ADSC-Exos.
Fig. 2: ADSC-Exos promote skin wound healing.
Fig. 3: ADSC-Exos promote HSF cell proliferation, migration and invasion via H19.
Fig. 4: MiR-19b, which is the target of H19, targets SOX9.
Fig. 5: ADSC-Exos inhibit miR-19b expression via H19, resulting in the promotion of HSF cell proliferation, migration and invasion.
Fig. 6: ADSC-Exos upregulate H19 to activate the Wnt/β-catenin pathway, resulting in the promotion of HSF cell proliferation, migration and invasion.
Fig. 7: ADSC-Exos promote skin wound healing via H19 in mice.

Data availability

All data generated during this study are available within the article.

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Acknowledgements

We would like to give our sincere gratitude to the reviewers for their constructive comments.

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Authors

Contributions

This study was designed by Li Qian and Li Pi. Xian-Xi Meng made great contribution to the data collection of this study, Li Qian and Bai-Rong Fang were responsible for the data analysis and ascertained the integrity as well as accuracy of the data. Li Qian and Li Pi prepared this manuscript. All author approved the final version of the manuscript to be published.

Corresponding author

Correspondence to Li Qian.

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The authors declare no competing interests.

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The study was approved by the Institutional Review Board of the First Affiliated Hospital of Kunming Medical University in strict accordance with Declaration of Helsinki. Written, informed consent was obtained from each participant. The animal protocol and experiment procedure were approved by the Institutional Animal Care and Use Committee of the First Affiliated Hospital of Kunming Medical University Hospital.

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Qian, L., Pi, L., Fang, BR. et al. Adipose mesenchymal stem cell-derived exosomes accelerate skin wound healing via the lncRNA H19/miR-19b/SOX9 axis. Lab Invest (2021). https://doi.org/10.1038/s41374-021-00611-8

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