标题：Integrin beta 1 in Adipose-Derived Stem Cells Accelerates Wound Healing via Activating PI3K/AKT Pathway
作者：Wang, Qihong; Zhang, Na; Hu, Lihua; Xi, Yong; Mi, Wenxin; Ma, Yindong
作者机构：[Wang, Qihong; Zhang, Na] Shandong Univ, Jinan Cent Hosp, Dept Urol Surg, 105 Jiefang Rd, Jinan 250013, Shandong, Peoples R China.; [Hu, Lihua] Taia 更多
通讯作者地址：Ma, YD (corresponding author), Shandong Univ, Jinan Cent Hosp, Dept Burn & Plast Surg, 105 Jiefang Rd, Jinan 250013, Shandong, Peoples R China.
来源：TISSUE ENGINEERING AND REGENERATIVE MEDICINE
关键词：Integrin beta 1; Adipose-derived stem cells; Refractory wounds; PI3K;; AKT
摘要：Background: This study aims to investigate the effect of integrin beta 1 on wound healing induced by adipose-derived stem cells (ADSCs), as well as the corresponding mechanism. Methods: Integrin beta 1 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-kappa B and ERK signaling pathways. The effects of integrin beta 1 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 beta 1 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 beta 1 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 beta 1 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.