Sung Jong-Hyuk, An Hyo-Sun, Jeong Jin-Hyun, Shin Soyoung, Song Seung Yong
College of Pharmacy, Yonsei University, Incheon, Republic of Korea; STEMORE Co. Ltd., Incheon, Republic of Korea; College of Pharmacy, Wonkwang University, Iksan, Republic of Korea; Institute for Human Tissue Restoration, Department of Plastic and Reconstructive Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
College of Pharmacy, Yonsei University, Incheon, Republic of Korea; STEMORE Co. Ltd., Incheon, Republic of Korea; College of Pharmacy, Wonkwang University, Iksan, Republic of Korea; Institute for Human Tissue Restoration, Department of Plastic and Reconstructive Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
Stem Cells Transl Med. 2015 Jul;4(7):789-99. doi: 10.5966/sctm.2015-0009. Epub 2015 May 13.
: Because adipose-derived stem cells (ASCs) are usually expanded to acquire large numbers of cells for therapeutic applications, it is important to increase the production yield and regenerative potential during expansion. Therefore, a tremendous need exists for alternative ASC stimuli during cultivation to increase the proliferation and adipogenic differentiation of ASCs. The present study primarily investigated the involvement of megestrol acetate (MA), a progesterone analog, in the stimulation of ASCs, and identifies the target receptors underlying stimulation. Mitogenic and adipogenic effects of MA were investigated in vitro, and pharmacological inhibition and small interfering (si) RNA techniques were used to identify the molecular mechanisms involved in the MA-induced stimulation of ASCs. MA significantly increased the proliferation, migration, and adipogenic differentiation of ASCs in a dose-dependent manner. Glucocorticoid receptor (GR) is highly expressed compared with other nuclear receptors in ASCs, and this receptor is phosphorylated after MA treatment. MA also upregulated genes downstream of GR in ASCs, including ANGPTL4, DUSP1, ERRF11, FKBP5, GLUL, and TSC22D3. RU486, a pharmacological inhibitor of GR, and transfection of siGR significantly attenuated MA-induced proliferation, migration, and adipogenic differentiation of ASCs. Although the adipogenic differentiation potential of MA was inferior to that of dexamethasone, MA had mitogenic effects in ASCs. Collectively, these results indicate that MA increases the proliferation, migration, and adipogenic differentiation of ASCs via GR phosphorylation.
Magestrol acetate (MA) increases the proliferation, migration, and adipogenic differentiation of adipose-derived stem cells (ASCs) via glucocorticoid receptor phosphorylation. Therefore, MA can be applied to increase the production yield during expansion and can be used to facilitate adipogenic differentiation of ASCs.
由于脂肪来源干细胞（ASC）通常需要扩增以获得大量用于治疗应用的细胞，因此在扩增过程中提高产量和再生潜力很重要。因此，在培养过程中迫切需要替代的ASC刺激物来增加ASC的增殖和成脂分化。本研究主要调查了醋酸甲地孕酮（MA）（一种孕酮类似物）在刺激ASC中的作用，并确定了刺激背后的靶受体。在体外研究了MA的促有丝分裂和成脂作用，并使用药理学抑制和小干扰（si）RNA技术来确定MA诱导的ASC刺激所涉及的分子机制。MA以剂量依赖性方式显著增加了ASC的增殖、迁移和成脂分化。与ASC中的其他核受体相比，糖皮质激素受体（GR）高度表达，并且该受体在MA处理后被磷酸化。MA还上调了ASC中GR下游的基因，包括ANGPTL4、DUSP1、ERRF11、FKBP5、GLUL和TSC22D3。GR的药理学抑制剂RU486和siGR转染显著减弱了MA诱导的ASC增殖、迁移和成脂分化。尽管MA的成脂分化潜力低于地塞米松，但MA在ASC中具有促有丝分裂作用。总体而言，这些结果表明MA通过GR磷酸化增加了ASC的增殖、迁移和成脂分化。
醋酸甲地孕酮（MA）通过糖皮质激素受体磷酸化增加脂肪来源干细胞（ASC）的增殖、迁移和成脂分化。因此，MA可用于在扩增过程中提高产量，并可用于促进ASC的成脂分化。
