Stromal cell-derived factor 1alpha reduces senescence of endothelial progenitor subpopulation in lectin-binding and DiLDL-uptaking cell through telomerase activation and telomere elongation.
Recent studies have suggested that reduced endothelial progenitor subpopulation in lectin-binding and DiLDL-uptaking cell (EPC subpopulation) number and activity was associated with EPC subpopulation senescence that involved telomerase activity and telomere length. Stromal cell-derived factor-1alpha (SDF-1alpha) has been shown to augment a variety of cellular functions of EPC subpopulation and subsequently contribute to ischemic neovascularization. Therefore, we investigated whether SDF-1alpha might be able to prevent senescence of EPC subpopulation and also investigated the effects of SDF-1alpha on the telomerase activity and telomere length. EPC subpopulation were isolated from peripheral blood and characterized. After ex vivo prolonged cultivation, EPC subpopulation became senescent as determined by acidic beta-galactosidase staining. SDF-1alpha dose-dependently inhibited the onset of EPC subpopulation senescence. Moreover, SDF-1alpha increased proliferation and colony-forming activity of EPC subpopulation. SDF-1alpha also increased telomerase activity and telomere length, which was accompanied with upregulation of the catalytic subunit, telomerase reverse transcriptase (TERT). Whereas these effects of SDF-1alpha on telomerase activity and expression of hTERT mRNA were significantly attenuated by CXCR4-specific peptide antagonist (AMD3100) and phosphoinositide 3-kinase (PI3K) inhibitor (LY294002). In conclusions, SDF-1alpha delays the onset of EPC subpopulation senescence, which may be related to the activation of telomerase and elongation of telomere length. The inhibition of EPC subpopulation senescence and induction of EPC subpopulation proliferation by SDF-1alpha in vitro may importantly improve the functional activity of EPC subpopulation for potential cell therapy.
Department of Cardiovascular Diseases, Biomedical Research (Therapy) Center, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, PR China.
Hao
H
Zheng
Cheng-Ji
CJ
Shen
Fu-Yu
FY
Qiu
Yan-Bo
YB
Zhao
Guo-Sheng
GS
Fu
D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*
D054377:Chemokine CXCL12; D037102:Lectins; D012333:RNA, Messenger; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C509186:TERT protein, human; D019098:Telomerase