title: Suppression of androgen receptor enhances the self-renewal of mesenchymal stem cells through elevated expression of EGFR.
abstract: 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.
authors: Department of Pathology, University of Rochester Medical Center, Rochester, NY, USA.
authors: Chiung-Kuei
authors: CK
authors: Huang
authors: Meng-Yin
authors: MY
authors: Tsai
authors: Jie
authors: J
authors: Luo
authors: Hong-Yo
authors: HY
authors: Kang
authors: Soo Ok
authors: SO
authors: Lee
authors: Chawnshang
authors: C
authors: Chang
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D059002:Androgen Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005485:Flutamide / Q000031:analogs & derivatives / Q000494:pharmacology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D059002:Androgen Receptor Antagonists; D011944:Receptors, Androgen; C014290:hydroxyflutamide; D005485:Flutamide; C541485:EGFR protein, mouse; D066246:ErbB Receptors