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Apigenin accelerates wound healing in diabetic mice by promoting macrophage M2-type polarization via increasing miR-21 expression

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Abstract

The alteration of inflammatory phenotype by macrophage polarization plays an important role in diabetic wound repair. Apigenin has been reported to be anti-inflammatory and promote tissue repair; however, whether it regulates macrophage polarization to participate in diabetic wound repair remains to be investigated. We found that apigenin promoted miR-21 expression in LPS-stimulated RAW264.7 cells, inhibited cellular M1-type factor TNF-α and IL-1β secretion and increased M2-type factor IL-10 and TGF-β secretion, and accelerated macrophage conversion from M1 type to M2 type, whereas this protective effect of apigenin was counteracted by a miR-21 inhibitor. Moreover, we established a macrophage-HUVECs cell in vitro co-culture system and found that apigenin accelerated the migration, proliferation, and VEGF secretion of HUVECs by promoting macrophage miR-21 expression. Further, mechanistic studies revealed that this was mediated by the TLR4/Myd88/NF-κB axis. In in vivo study, diabetic mice had significantly delayed wound healing compared to non-diabetic mice, accelerated wound healing in apigenin-treated diabetic mice, and decreased M1-type macrophages and increased M2-type macrophages in wound tissues.

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Data availability

The datasets used during the present study are available from the corresponding author upon reasonable request.

Abbreviations

LPS:

Lipopolysaccharide

IFN-γ:

Interferon-γ

IL-4:

Interleukin-4

COX-2:

Cyclooxygenase-2

HUVECs:

Human umbilical vein endothelial cells

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Acknowledgements

I would like to express my gratitude to all those helped me during the writing of this thesis. I acknowledge the help of my colleagues, Lijun Wu; they have offered me suggestion in academic studies.

Funding

This study was supported by Suzhou People’s Livelihood Science and Technology Project (SYS2020105); Construction of key clinical specialties for the Suzhou Municipal “Strengthening Health through Science and Education” Funding Project; Hospital Research Fund (SDFEYBS1805, SDFEYGJ2013, XKTJ-HRC20210015); Suzhou Science and Technology Development Project (SYS2020105, SKJY2021078 and 2022SS43); the Special Project of “Technological Innovation” Project of CNNC Medical Industry Co. Ltd (ZHYLZD2021002); Project of State Key Laboratory of Radiation Medicine and Protection, Soochow University, (No. GZK1202244); and the CNNC Elite Talent Program.

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Author notes

  1. Ke Li and Lijun Wu have contributed equally to this work.

Authors and Affiliations

  1. Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China

    Ke Li & Jingting Jiang

  2. Department of Burn and Plastic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China

    Ke Li

  3. Department of Plastic and Aesthetic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China

    Lijun Wu

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  1. Ke Li
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Contributions

KL and JJ: designed the experiments. KL and LW: performed the experimental LW and JJ: provided statistical analysis and figures for the manuscript. KL: wrote the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jingting Jiang.

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11010_2023_4885_MOESM1_ESM.tif

Supplementary file1 (TIF 2342 kb)— The secretion of inflammatory factors in non-activated RAW264.7 cells. The RAW264.7 cells (M0 macrophages) were left untreated or treated with apigenin alone. A&B&C&D. The secretion levels of TNF-α, IL-1β, IL-10, and TGF-β in RAW264.7 cells.

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Li, K., Wu, L. & Jiang, J. Apigenin accelerates wound healing in diabetic mice by promoting macrophage M2-type polarization via increasing miR-21 expression. Mol Cell Biochem (2024). https://doi.org/10.1007/s11010-023-04885-y

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