Tian Xia-Qiu, Yang Yue-Jin, Li Qing, Huang Pei-Sen, Li Xiang-Dong, Jin Chen, Qi Kang, Jiang Lei-Pei, Chen Gui-Hao
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
Cell Physiol Biochem. 2016;38(3):909-25. doi: 10.1159/000443044. Epub 2016 Feb 29.
BACKGROUND/AIMS: Poor viability of transplanted mesenchymal stem cells (MSCs) within the ischemic heart limits their therapeutic potential for cardiac repair. Globular adiponectin (gAPN) exerts anti-apoptotic effects on several types of stem cells. Herein, we investigated the effect of gAPN on the MSCs against apoptosis induced by hypoxia and serum deprivation (H/SD).
MSCs exposed to H/SD conditions were treated with different concentrations of gAPN. To identify the main type of receptor, MSCs were transfected with siRNA targeting adiponectin receptor 1 or 2 (AdipoR1 or AdipoR2). To elucidate the downstream pathway, MSCs were pre-incubated with AMPK inhibitor Compound C. Apoptosis, caspase-3 activity and mitochondrial membrane potential were evaluated.
H/SD-induced MSCs apoptosis and caspase-3 activation were attenuated by gAPN in a concentration-dependent manner. gAPN increased Bcl-2 and decreased Bax expressions. The loss of mitochondrial membrane potential induced by H/SD was also abolished by gAPN. The protective effect of gAPN was significantly attenuated after the knockdown of AdipoR1 rather than AdipoR2. Moreover, Compound C partly suppressed the anti-apoptotic effect of gAPN.
gAPN inhibits H/SD-induced apoptosis in MSCs via AdipoR1-mediated pathway, possibly linked to the activation of AMPK. gAPN may be a novel survival factor for MSCs in the ischemic engraftment environment.
背景/目的：移植的间充质干细胞（MSC）在缺血心脏中的低存活率限制了其心脏修复的治疗潜力。球形脂联素（gAPN）对几种类型的干细胞具有抗凋亡作用。在此，我们研究了gAPN对缺氧和血清剥夺（H/SD）诱导的MSC凋亡的影响。
将暴露于H/SD条件下的MSC用不同浓度的gAPN处理。为了确定主要的受体类型，用靶向脂联素受体1或2（AdipoR1或AdipoR2）的小干扰RNA（siRNA）转染MSC。为了阐明下游途径，将MSC与AMPK抑制剂化合物C预孵育。评估凋亡、半胱天冬酶-3活性和线粒体膜电位。
gAPN以浓度依赖的方式减轻了H/SD诱导的MSC凋亡和半胱天冬酶-3激活。gAPN增加了Bcl-2表达并降低了Bax表达。gAPN也消除了H/SD诱导的线粒体膜电位丧失。敲低AdipoR1而不是AdipoR2后，gAPN的保护作用显著减弱。此外，化合物C部分抑制了gAPN的抗凋亡作用。
gAPN通过AdipoR1介导的途径抑制H/SD诱导的MSC凋亡，可能与AMPK的激活有关。gAPN可能是缺血植入环境中MSC的一种新型存活因子。
