Qihong Wang1, Na Zhang1, Lihua Hu2, Yong Xi3, Wenxin Mi4, Yindong Ma5. 1. Department of Urology Surgery, Jinan Central Hospital Affiliated to Shandong University, No. 105 Jiefang Road, Lixia District, Jinan, 250013, Shandong Province, China. 2. Department of Burn, Tai'an Hospital of Traditional Chinese Medicine, No. 58 Dongyue Avenue, Taishan District, Tai'an, 271000, Shandong Province, China. 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. 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. 5. Department of Burn and Plastic Surgery, Jinan Central Hospital Affiliated to Shandong University, No. 105 Jiefang Road, Lixia District, Jinan, 250013, Shandong Province, China. Yindongmayd@163.com.
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.
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.
Authors: Matti Peura; Jozef Bizik; Pertteli Salmenperä; Ariel Noro; Matti Korhonen; Tommi Pätilä; Antti Vento; Antti Vaheri; Riitta Alitalo; Jyrki Vuola; Ari Harjula; Esko Kankuri Journal: Wound Repair Regen Date: 2009 Jul-Aug Impact factor: 3.617
Authors: Maria H M Lima; Andréa M Caricilli; Lélia L de Abreu; Eliana P Araújo; Fabiana F Pelegrinelli; Ana C P Thirone; Daniela M Tsukumo; Ana Flávia M Pessoa; Marinilce F dos Santos; Maria A de Moraes; José B C Carvalheira; Lício A Velloso; Mario J A Saad Journal: PLoS One Date: 2012-05-25 Impact factor: 3.240