Follistatin-like 1-engineered mesenchymal stem cells prevent myocardial ischemic reperfusion injury
- Author:
- No author available
- Journal Title:
- National Medical Journal of China
- Issue:
- 25
- DOI:
- 10.3760/cma.j.issn.0376-2491.2016.25.013
- Key Word:
- 卵泡抑素相关蛋白质类;间质干细胞;心肌再灌注损伤;Follistatin-related proteins;Mesenchymal stem cell;Myocardial reperfusion injury
Abstract： Objective To investigate the role of follistatin-like protein 1 (FSTL1) on bone marrow mesenchymal stem cells (BM-MSCs)-mediated cardioprotection during myocardial ischemia/reperfusion injury.Methods Rat bone marrow mesenchymal stem cells were isolated by whole bone marrow adherence method in vitro.A total of 60 Wistar rats were randomly divided into 4 groups:control group,ischemic / reperfusion injury (IRI) group,ischemia/reperfusion injury group treated with natural BM-MSCs (IRI + MSC group),ischemia/reperfusion injury group treated with BM-MSCs which did not contain FSTL1 (IRI + MSC FSTL1 siRNA group).Survival analysis was used to analyze survival time of rats,besides,expression of FSTL1 was detected by Western blotting.Myocardial pathological changes were detected by Hematoxylin and Eosin (HE) staining.Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) and enzyme-linked immunosorbent assay (ELISA) were used to determine the associated biomarkers and apoptosis 7 days after operation.Results Compared with IRI group,rats in IRI + MSC group had a higher survival rate and lived longer.Meanwhile,IRI + MSC group had higher FSTL1 expression in blood and myocardial tissues than IRI group.Control group showed significantly lower apoptosis rate of myocardial cells [(1.4 ± 0.1) ％ vs (29.8 ± 4.5) ％,P ＜ 0.05],less histological changes and infarction areas (0 vs 24.48 ± 4.27,P ＜ 0.05) than IRI group.Compared with IRI group,IRI + MSC group had an improvement of apoptosis rate [(4.2 ± 0.3) ％ vs (29.8 ± 4.5) ％,P ＜ 0.05],less histological injury and infarction areas (15.12 ± 3.82 vs 24.48 ± 4.27,P ＜ 0.01).IRI + MSC group had lower expression of LDH,MDA,CK and higher expression of SOD than IRI group (P ＜ 0.05).However,IRI + MSC FSTL1 siRNA group showed weaker protection of myocardial cells than IRI + MSC group after knockdown of FSTL1 (P ＜ 0.05).Conclusion FSTL1,which was secreted by BM-MSCs,plays a protective role in myocardial IRI.
- [1]张美齐,吴爱萍,沈晔,等.左卡尼汀联合比索洛尔对内质网应激介导的心肺复苏后大鼠心肌损伤的影响[J].2015,(19).
- [2]武令启,白海,王存帮,等.间充质干细胞对异体B淋巴细胞增殖和凋亡的影响[J].2008,(36).
- [3]Leistner DM,Zeiher AM.Novel avenues for cell therapy in acute myocardial infarction.[J].2012,110(2).
- [4]Hwang KC,Lee M,Kim SH,etc.Hypoxia-inducible vascular endothelial growth factor-engineered mesenchymal stem cells prevent myocardial ischemic injury.[J].2011,19(4).
- [5]Hua,P.,Liu,L.-B.,Liu,J.-L.,etc.Inhibition of apoptosis by knockdown of caspase-3 with siRNA in rat bone marrow mesenchymal stem cells[J].2013,238(9).
- [6]Peng, Yu,Jing, Zhang,Shuchun, Yu,etc.Protective Effect of Sevoflurane Postconditioning against Cardiac Ischemia/Reperfusion Injury via Ameliorating Mitochondrial Impairment, Oxidative Stress and Rescuing Autophagic Clearance.[J].2015,10(8).
- [7]Amthor H.,Nose K.,Connolly DJ.,etc.Cloning and Early Dorsal Axial Expression of Flik, a Chick Follistatin-Related Gene - Evidence for Involvement in Dorsalization Neural Induction[J].1996,178(2).
- [8]Pimentel DR,Ouchi N,Sato K,etc.Follistatin-like 1 is an Akt-regulated cardioprotective factor that is secreted by the heart.[J].2008,117(24).
- [9]Hauser PV,Carvalhosa R,Bussolati B,etc.Contribution of stem cells to kidney repair.[J].2009,4(1).
- [10]Jingyue, Xu,Xin, Qi,Jianfeng, Gong,etc.Fstl1 antagonizes BMP signaling and regulates ureter development.[J].2012,7(4).
- [11]Su, Ni,Kaisong, Miao,Xianju, Zhou,etc.The involvement of follistatin-like protein 1 in osteoarthritis by elevating NF-κB-mediated inflammatory cytokines and enhancing fibroblast like synoviocyte proliferation.[J].2015,17.
- [12]Enrique, Lara-Pezzi,Ana, Dopazo,Miguel, Manzanares.Understanding cardiovascular disease: a journey through the genome (and what we found there).[J].2012,5(4).
- [13]Tomoda J,Kusachi S,Ikeda M,etc.Association of circulating levels of leptin and adiponectin with metabolic syndrome and coronary heart disease in patients with various coronary risk factors.[J].2011,52(1).
- [14]Jing, Zhang,Chen, Wang,Shuchun, Yu,etc.Sevoflurane postconditioning protects rat hearts against ischemia-reperfusion injury via the activation of PI3K/AKT/mTOR signaling.[J].2014,4.
- [15]Tanaka M,Ozaki S,Osakada F,etc.Cloning of follistatin-related protein as a novel autoantigen in systemic rheumatic diseases.[J].1998,10(9).
- [16]Eschenhagen, Thomas,Peter, Christoph,Fedak, Paul W. M.,etc.Hepatocyte Growth Factor or Vascular Endothelial Growth Factor Gene Transfer Maximizes Mesenchymal Stem Cell-Based Myocardial Salvage After Acute Myocardial Infarction[J].2009,120(11 Suppl.1).
- [17]Abdulaziz Al-Khaldi,Hilal Al-Sabti,Jacques Galipeau,etc.Therapeutic angiogenesis using autologous bone marrow stromal cells: improved blood flow in a chronic limb ischemia model[J].2003,75(1).
- [18]Hui, Wu,Ming, Ye,Jun, Yang,etc.Nicorandil Protects the Heart from Ischemia/Reperfusion Injury by Attenuating Endoplasmic Reticulum Response-induced Apoptosis Through PI3K/Akt Signaling Pathway.[J].2015,35(6).