title: Globular Adiponectin Inhibits the Apoptosis of Mesenchymal Stem Cells Induced by Hypoxia and Serum Deprivation via the AdipoR1-Mediated Pathway.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Xia-Qiu
authors.initials: XQ
authors.lastname: Tian
authors.forename: Yue-Jin
authors.initials: YJ
authors.lastname: Yang
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Pei-Sen
authors.initials: PS
authors.lastname: Huang
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Li
authors.forename: Chen
authors.initials: C
authors.lastname: Jin
authors.forename: Kang
authors.initials: K
authors.lastname: Qi
authors.forename: Lei-Pei
authors.initials: LP
authors.lastname: Jiang
authors.forename: Gui-Hao
authors.initials: GH
authors.lastname: Chen
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D054419:Receptors, Adiponectin / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D052242:Adiponectin; D016895:Culture Media, Serum-Free; D011720:Pyrazoles; D011743:Pyrimidines; D034741:RNA, Small Interfering; D054419:Receptors, Adiponectin; C504339:adiponectin receptor 1, rat; C506573:adiponectin receptor 2, rat; C516138:dorsomorphin; C505410:Casp3 protein, rat; D053148:Caspase 3