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Exosomes derived from adipose tissues accelerate fibroblasts and keratinocytes proliferation and cutaneous wound healing via miR-92a/Hippo-YAP axis

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Abstract

Delayed wound healing is an urgent clinical issue. Cellular communication involving exosome-borne cargo such as miRNA is a critical mechanism involved in wound healing. This study isolated and identified human adipose tissue-derived exosomes (Exo-ATs). The specific effects of Exo-ATs on keratinocytes and fibroblasts were examined. Enriched miRNAs in Exo-ATs were analyzed, and miR-92a-3p was selected. The transfer of Exo-ATs-derived miR-92a-3p to keratinocytes and fibroblasts was verified. miR-92a-3p binding to LATS2 was examined and the dynamic effects of the miR-92a-3p/LATS2 axis were investigated. In a dorsal skin wound model, the in vivo effects of Exo-ATs on wound healing were examined. Exo-AT incubation increased keratinocytes and fibroblast proliferation, migration, and extracellular matrix (ECM) accumulation. miR-92a-3p, enriched in Exo-ATs, could be transferred to keratinocytes and fibroblasts, resulting in enhanced proliferation, migration, and ECM accumulation. Large tumor suppressor kinase 2 (LATS2) was a direct target of miR-92a-3p. miR-92a-3p inhibitor effects on keratinocytes and fibroblasts could be partially reversed by LATS2 knockdown. In a dorsal skin wound model, Exo-ATs accelerated wound healing through enhanced cell proliferation, collagen deposition, re-epithelialization, and YAP/TAZ activation. In conclusion, Exo-ATs improve skin wound healing by promoting keratinocyte and fibroblast migration and proliferation and collagen production by fibroblast, which could be partially eliminated by miR-92a inhibition through its downstream target LATS2 and the YAP/TAZ signaling.

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Data availability

The data generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Funding

This work has been supported by the National Natural Science Foundation of China (82800952), the Natural Science Foundation of Hunan Province, China (2021JJ30987), and the Key Research and Development Project of Hunan Province, China (2020sk2056).

Author information

Author notes

  1. Zifei Shao and Jinghao Xu contributed equally to this study.

Authors and Affiliations

  1. Department of Oral & Maxillofacial Surgery, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, 410000, China

    Zifei Shao, Jinghao Xu, Xiang Wang, Yuxi Zhou, Yujing Wang, Yiyang Li & Kun Li

  2. Hunan Clinical Research Center of Oral Major Diseases and Oral Health & Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South University, Changsha, 410008, Hunan, China

    Zifei Shao, Jinghao Xu, Xiang Wang, Yuxi Zhou, Yujing Wang, Yiyang Li & Kun Li

  3. Department of Stomatology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, 215125, Jiangsu, China

    Jianping Zhao

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  1. Zifei Shao
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Contributions

ZF S and JH X performed the experiments and wrote the main manuscript text. X W performed the experiments.YX Z coordinated the study. YJ W and YY L assisted with the experiments. JP Z and K L conceived the study, designed the experiments, and revised the paper. All the authors have reviewed and approved the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding authors

Correspondence to Jianping Zhao or Kun Li.

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All the procedures were approved by the Ethics Committee of Xiangya Stomatological Hospital of Central South University (no.20180006).

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The authors declare no competing interests.

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Key points

1. Exo-AT derived from human adipose tissue was isolated and identified in this study.

2. Exo-AT enhances proliferation, migration, and ECM accumulation in keratinocytes and fibroblasts through miR-92a-3p transfer.

3. Exo-AT promotes wound healing by accelerating cell proliferation, collagen deposition, epithelialization, and YAP/TAZ activation.

4. MiR-92a-3p/LATS2 axis plays a key role in Exo-AT-mediated effects on keratinocytes and fibroblasts.

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Shao, Z., Xu, J., Wang, X. et al. Exosomes derived from adipose tissues accelerate fibroblasts and keratinocytes proliferation and cutaneous wound healing via miR-92a/Hippo-YAP axis. J Physiol Biochem 80, 189–204 (2024). https://doi.org/10.1007/s13105-023-00996-8

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  • DOI: https://doi.org/10.1007/s13105-023-00996-8

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