脂肪来源干细胞中的整合素 β1 通过激活 PI3K/AKT 通路加速伤口愈合。
Integrin β1 in Adipose-Derived Stem Cells Accelerates Wound Healing via Activating PI3K/AKT Pathway.
机构信息
Department of Urology Surgery, Jinan Central Hospital Affiliated to Shandong University, No. 105 Jiefang Road, Lixia District, Jinan, 250013, Shandong Province, China.
Department of Burn, Tai'an Hospital of Traditional Chinese Medicine, No. 58 Dongyue Avenue, Taishan District, Tai'an, 271000, Shandong Province, China.
出版信息
Tissue Eng Regen Med. 2020 Apr;17(2):183-192. doi: 10.1007/s13770-019-00229-4. Epub 2020 Mar 21.
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.
背景
本研究旨在探讨整合素β1对脂肪来源干细胞（ADSCs）诱导的伤口愈合的影响及其相应的机制。
方法
过表达 ADSC 中的整合素β1。然后，采用流式细胞术和 Transwell 室技术分别测量内皮样分化（以内皮细胞标志物 CD31 表示）和细胞迁移。采用 Western blot 检测 PI3K/AKT、NF-κB 和 ERK 信号通路的激活。进一步在慢性难治性伤口大鼠模型中评估整合素β1过表达对愈合时间、愈合率和成纤维细胞数量的影响。
结果
整合素β1的过表达增加了 CD31 内皮样细胞（约 3.6 倍），促进了细胞迁移（约 1.9 倍），并增强了 PI3K（p-PI3K；约 2.1 倍）和 AKT（p-AKT；约 2.2 倍）的激活。当用 LY294002 抑制 PI3K/AKT 通路时，这些作用均减弱。此外，在大鼠伤口模型实验中，整合素β1过表达明显缩短了愈合时间（约 0.41 倍），增加了愈合率（第 7、14 和 21 天分别约为 2.7、2.8 和 1.6 倍），并增加了成纤维细胞的数量（第 21 天约为 3.1 倍）。所有这些差异均具有统计学意义（p<0.05）。
结论
整合素β1通过激活 PI3K/AKT 通路促进 ADSC 的迁移和内皮样分化，从而增强 ADSC 在促进伤口愈合中的功能。
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