Suppression of androgen receptor enhances the self-renewal of mesenchymal stem cells through elevated expression of EGFR.
Suppression of androgen receptor enhances the self-renewal of mesenchymal stem cells through elevated expression of EGFR.
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DOI：
10.1016/j.bbamcr.2013.01.007
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发表时间：
2013-05
影响因子：
5.1
通讯作者：
Chang, Chawnshang
中科院分区：
文献类型：
--
作者：
Huang, Chiung-Kuei;Tsai, Meng-Yin;Luo, Jie;Kang, Hong-Yo;Lee, Soo Ok;Chang, Chawnshang
关键词：
骨髓间充质干细胞（BM-MSCs）已广泛应用于心肌梗死、肝硬化、神经退行性疾病、成骨细胞等疾病的临床研究。虽然大多数研究表明BM-MSCs移植确实能起到暂时缓解和短期治疗效果，但最终所有症状都会复发，因此通过提高BM-MSCs的自我更新能力或提高其存活率来提高移植的治疗效果是至关重要的。在此，我们证明了从雄激素受体（AR）敲除小鼠中分离的BM-MSCs和脂肪细胞来源的间充质干细胞（ADSCs）比从野生型小鼠中获得的具有更高的自我更新能力。MSC细胞系中AR的敲低表现出类似的结果。机械解剖研究表明，AR的消耗导致Erk和Akt信号通路的激活，通过表皮生长因子受体（EGFR）激活或通路介导BM-MSCs的更高自我更新。使用ASC-J 9 ®（AR降解增强剂）、羟基氟替卡松（AR拮抗剂）和AR-siRNA靶向AR信号均导致MSC的自我更新增强，这表明未来可能在治疗方法中使用这些抗AR剂。
Bone marrow derived mesenchymal stem cells (BM-MSCs) have been widely applied in several clinical trials of diseases, such as myocardial infarction, liver cirrhosis, neurodegenerative disease, and osteogenesis imperfecta. Although most studies demonstrated that transplantation of BM-MSCs did exert a temporary relief and short-term therapeutic effects, eventually all symptoms recur, therefore it is essential to improve the therapeutic efficacy of transplantation by either elevating the self-renewal of BM-MSCs or enhancing their survival rate. Herein we demonstrated that the BM-MSCs and adipocyte derived mesenchymal stem cells (ADSCs) isolated from the androgen receptor (AR) knockout mice have higher self-renewal ability than those obtained from the wild-type mice. Knockdown of AR in MSC cell lines exhibited similar results. Mechanistic dissection studies showed that the depletion of AR resulted in activation of Erk and Akt signaling pathways through epidermal growth factor receptor (EGFR) activation or pathway to mediate higher self-renewal of BM-MSCs. Targeting AR signals using ASC-J9® (an AR degradation enhancer), hydroxyflutamide (antagonist of AR), and AR-siRNA all led to enhanced self-renewal of MSCs, suggesting the future possibility of using these anti-AR agents in therapeutic approaches.
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DOI：
10.1073/pnas.1036475100
发表时间：
2003-05-13
影响因子：
11.1
作者：
Bonyadi, M;Waldman, SD;Stanford, WL
通讯作者：
Stanford, WL
影响因子：
3.1
作者：
Crisostomo, Paul R.;Wang, Meijing;Meldrum, Daniel R.
通讯作者：
Meldrum, Daniel R.
影响因子：
5.8
作者：
Eugène, D;Djemli, A;Van Vliet, G
通讯作者：
Van Vliet, G
影响因子：
11.4
作者：
Matsuda, T;Nakamura, T;Yokota, T
通讯作者：
Yokota, T
影响因子：
82.9
作者：
Horwitz, EM;Prockop, DJ;Brenner, MK
通讯作者：
Brenner, MK