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Exosomal microRNA-125a-3p from human adipose-derived mesenchymal stem cells promotes angiogenesis of wound healing through inhibiting PTEN

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Abstract

Angiogenesis plays a key in the process of tissue repair and wound healing. Human adipose-derived mesenchymal stem cells (HADSCs) have been found to act a promotion role during angiogenesis. Moreover, miR-125a-3p in HADSCs could promote the angiogenesis of HUVECs, but their specific mechanism in wound healing needs further study. Western blotting and qRT-PCR were used for detecting the protein and mRNA level, respectively. Exosomes were isolated successfully, and transmission electron microscope was used to identify exosomes. Angiogenesis, cell migration, and proliferation were detected with tube formation, wound healing, and MTT assays. The interactions of miR-125a-3p and PTEN were validated using dual-luciferase reporter assay. Animal model was used to evaluate the effect of miR-125a-3p on wound healing. HADSCs-exosome remarkably promoted the viability, migration, and angiogenesis of HUVECs. Knockdown of miR-125a-3p in HADSCs could inhibit the effect of HADSCs–exosome, while overexpression of miR-125a-3p could further promote the effect of HADSCs–exosome on HUVECs. MiR-125a-3p from HADSCs–exosome inhibited the expression of PTEN in HUVECs. Knockdown of PTEN promoted the viability, migration, and angiogenesis of HUVECs and reversed the effect of miR-125a-3p knockdown on HUVECs. Finally, miR-125a-3p from HADSCs–exosome could promote wound healing and angiogenesis in mice by inhibiting PTEN in mice wound granulation tissues. MiR-125a-3p from the HADSCs–exosome promoted the wound healing and angiogenesis, and these effects were achieved through regulating PTEN. This study may provide a new thought for the treatment and prevention of tissue repair.

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Data availability

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

Abbreviations

HADSCs:

Human adipose-derived mesenchymal stem cells

TEM:

Transmission electron microscope

MSCs:

Mesenchymal stem cells

HADSCs–exosome:

Exosome derived from human adipose-derived mesenchymal stem cells

DLL4:

Delta-like 4

HUVEC:

Human umbilical vein endothelial cells

ATCC:

American type culture collection

HE:

Hematoxylin–eosin

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Authors and Affiliations

  1. Department of Burn and Plastic Surgery, The Second Xiangya Hospital, Central South University, No. 139 Renmin Road, Furong District, Changsha, 410011, Hunan Province, China

    Li Pi, Li Yang, Bai-Rong Fang, Xian-Xi Meng & Li Qian

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  1. Li Pi
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  2. Li Yang
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Contributions

Guarantor: LQ; concepts: LQ; study design: LQ; clinical studies: LP; experimental studies: XXM; data acquisition: LY; data analysis: LY, BRF; preparation: BRF; editing: XXM; manuscript review: LP. All the authors approved for the final version.

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Correspondence to Li Qian.

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Pi, L., Yang, L., Fang, BR. et al. Exosomal microRNA-125a-3p from human adipose-derived mesenchymal stem cells promotes angiogenesis of wound healing through inhibiting PTEN. Mol Cell Biochem 477, 115–127 (2022). https://doi.org/10.1007/s11010-021-04251-w

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