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Integrin β1 in Adipose-Derived Stem Cells Accelerates Wound Healing via Activating PI3K/AKT Pathway

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

This study aims to investigate the effect of integrin β1 on wound healing induced by adipose-derived stem cells (ADSCs), as well as the corresponding mechanism.

Methods:

Integrin β1 was overexpressed in ADSCs. Thereafter, flow cytometry and transwell chambers technology were used to measure the endothelial-like differentiation (CD31 as a biomarker of endothelial cell) and cell migration, respectively. Western blot was used to detect the activation of PI3K/AKT, NF-κB and ERK signaling pathways. The effects of integrin β1 overexpression on healing time, healing rate and fibroblast number were further evaluated in the rat models of chronic refractory wound.

Results:

The overexpression of integrin β1 increased CD31+ endothelial-like cells (about 3.6-fold), promoted cell migration (about 1.9-fold) and enhanced the activation of PI3K (p-PI3K; about 2.1-fold) and AKT (p-AKT; about 2.2-fold). These effects were all weakened when PI3K/AKT pathway was inhibited by LY294002 treatment. In addition, the experiments in rat wound models showed that integrin β1 overexpression obviously shortened healing time (approximately 0.41-fold), increased healing rate (about 2.7-fold, 2.8-fold and 1.6-fold at day 7, 14 and 21) and increased the number of fibroblasts (approximately 3.1-fold at day 21). All of the above differences were statistically significant (p < 0.05).

Conclusion:

Integrin β1 can promote the migration and endothelial-like differentiation of ADSCs by activating PI3K/AKT pathway and then enhance the function of ADSCs in promoting wound healing.

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Authors and Affiliations

  1. Department of Urology Surgery, Jinan Central Hospital Affiliated to Shandong University, No. 105 Jiefang Road, Lixia District, Jinan, 250013, Shandong Province, China

    Qihong Wang & Na Zhang

  2. Department of Burn, Tai’an Hospital of Traditional Chinese Medicine, No. 58 Dongyue Avenue, Taishan District, Tai’an, 271000, Shandong Province, China

    Lihua Hu

  3. Department of Surgery, The Forth People’s Hospital of Zhangqiu District in Jinan, No. 15 Zaoyuan Avenue, Zaoyuan Town, Zhangqiu District, Jinan, 250214, Shandong Province, China

    Yong Xi

  4. Department of Burn and Plastic Surgery, Jinan Central Hospital Affiliated to Shandong University, No. 105 Jiefang Road, Lixia District, Jinan, 250013, Shandong Province, China

    Wenxin Mi & Yindong Ma

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  1. Qihong Wang
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  2. Na Zhang
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  3. Lihua Hu
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  4. Yong Xi
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Correspondence to Yindong Ma.

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Ethical statement

The animal studies were performed after receiving approval of the Institutional Animal Care and Use Committee in Shandong University, China (No. ECAESDUSM 2016031).

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Wang, Q., Zhang, N., Hu, L. et al. Integrin β1 in Adipose-Derived Stem Cells Accelerates Wound Healing via Activating PI3K/AKT Pathway. Tissue Eng Regen Med 17, 183–192 (2020). https://doi.org/10.1007/s13770-019-00229-4

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  • DOI: https://doi.org/10.1007/s13770-019-00229-4

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