Stem cell antigen-1 (Sca-1) is a mouse glycosyl phosphatidylinositol-anchored protein and a cell surface marker found on hematopoietic stem cells (HSCs). Despite decades of study, its biological functions remain little known. Sca-1 is a typical marker of bone marrow-derived HSCs, it is also expressed by a mixture of tissue-resident stem, progenitor cells in nonhematopoietic organs. Endothelial progenitor cell (EPC) is a subtype of HSC and contributes to endothelial repair by homing in on locations of injury. Abnormal genetic methylation has been detected in smoking-related diseases. The present study aimed to investigate the lung function and histomorphology, the expression of Sca-1 gene in lung tissues, and bone marrow-derived EPCs in cigarette smoke extract (CSE)-induced emphysema mice, and to further determine whether Decitabine (Dec), the most widely used inhibitor of DNA methylation, could protect against the damages caused by CSE. The results of the present study demonstrated that Dec could partly protect against CSE-induced emphysema in mice, enhance Sca-1 expression in lung tissue, and bone marrow-derived EPCs. The results suggested that the depletion of the progenitor cell pool and DNA methylation of Sca-1 gene may be involved in the progression of emphysema in mice.
YutokuMGrossbergALPressmanD. A cell surface antigenic determinant present on mouse plasmacytes and only about half of mouse thymocytes. J Immunol1974; 112: 1774–81.
3.
SpangrudeGJHeimfeldSWeissmanIL. Purification and characterization of mouse hematopoietic stem cells. Science1988; 241: 58–62.
4.
OkadaSNakauchiHNagayoshiKNishikawaSMiuraYSudaT. In vivo and in vitro stem cell function of c-kit- and Sca-1-positive murine hematopoietic cells. Blood1992; 80: 3044–50.
5.
TamakiTAkatsukaAAndoKNakamuraYMatsuzawaHHottaTRoyRREdgertonVR. Identification of myogenic-endothelial progenitor cells in the interstitial spaces of skeletal muscle. J Cell Biol2002; 157: 571–7.
YangYGanYCaoJChenYHeZHLuoHCaiSXiangXDZhouRChenP. Decreased and dysfunctional circulating endothelial progenitor cells in patients with chronic obstructive pulmonary disease. Chin Med J (Engl)2013; 126: 3222–7.
10.
WangDWangJLiYHeZZhangY. The influence of anthracosis and p16 ink4a gene aberrant methylation on small-sized pulmonary adenocarcinoma. Exp Mol Pathol2011; 90: 131–6.
11.
PlimackERKantarjianHMIssaJP. Decitabine and its role in the treatment of hematopoietic malignancies. Leuk Lymphoma2007; 48: 1472–81.
12.
World Medical Association, American Physiological Society. Guiding principles for research involving animals and human beings. Am J Physiol Regul Integr Comp Physiol2002; 283: R281–3.
13.
ChenYHanaokaMChenPDromaYVoelkelNFKuboK. Protective effect of beraprost sodium, a stable prostacyclin analog, in the development of cigarette smoke extract-induced emphysema. Am J Physiol Lung Cell Mol Physiol2009; 296: L648–56.
14.
ZhangHChenPZengHZhangYPengHChenYHeZ. Protective effect of demethylation treatment on cigarette smoke extract-induced mouse emphysema model. J Pharmacol Sci2013; 123: 159–66.
15.
ZhangYCaoJChenYChenPPengHCaiSLuoHWuSJ. Intraperitoneal injection of cigarette smoke extract induced emphysema, and injury of cardiac and skeletal muscles in BALB/C mice. Exp Lung Res2013; 39: 18–31.
16.
He ZH, Chen P, Chen Y, Zhu YQ, He SD, Ye JR, Liu D, Yang Y. Dual effects of cigarette smoke extract on proliferation of endothelial progenitor cells and the protective effect of 5-aza-2'-deoxycytidine on EPCs against the damage caused by CSE. Biomed Res Int 2014;2014:640752.
17.
TousoulisDBriasoulisAVogiatziGValatsouAKourkoutiPPantopoulouAPapageorgiouNPerreaDStefanadisC. Infusion of lin-/sca-1+ and endothelial progenitor cells improves proinflammatory and oxidative stress markers in atherosclerotic mice. Int J Cardiol2013; 167: 1900–5.
18.
KojimaKOhhashiRFujitaYHamadaNAkaoYNozawaYDeguchiTItoM. A role for SIRT1 in cell growth and chemoresistance in prostate cancer PC3 and DU145 cells. Biochem Biophys Res Commun2008; 373: 423–8.
19.
KottonDNSummerRSSunXMaBYFineA. Stem cell antigen-1 expression in the pulmonary vascular endothelium. Am J Physiol Lung Cell Mol Physiol2003; 284: L990–6.
DevanesanAJLaughlanKAGirnHRHomer-VanniasinkamS. Endothelial progenitor cells as a therapeutic option in peripheral arterial disease. Eur J Vasc Endovasc Surg2009; 38: 475–81.
22.
LoebingerMRAguilarSJanesSM. Therapeutic potential of stem cells in lung disease: progress and pitfalls. Clin Sci (Lond)2008; 114: 99–108.
23.
CritserPJYoderMC. Endothelial colony-forming cell role in neoangiogenesis and tissue repair. Curr Opin Organ Transplant2010; 15: 68–72.
24.
KahlerCMWechselbergerJHilbeWGschwendtnerAColleselliDNiedereggerHBonebergEMSpizzoGWendelAGunsiliusEPatschJRHamacherJ. Peripheral infusion of rat bone marrow derived endothelial progenitor cells leads to homing in acute lung injury. Respir Res2007; 8: 50–50.
25.
IzzottiAD'AgostiniFLargheroPCartigliaCTravainiGBalanskyRSteeleVEDe FloraS. Upregulation of stem cell antigen-1 in the lung of neonatal mice exposed to environmental cigarette smoke. Oncol Rep2009; 22: 469–74.
26.
RauscherFMGoldschmidt-ClermontPJDavisBHWangTGreggDRamaswamiPPippenAMAnnexBHDongCTaylorDA. Aging, progenitor cell exhaustion, and atherosclerosis. Circulation2003; 108: 457–63.
27.
JieKEGoossensMHvan OostromOLilienMRVerhaarMC. Circulating endothelial progenitor cell levels are higher during childhood than in adult life. Atherosclerosis2009; 202: 345–7.
28.
LeeJSandfordAManPSinDD. Is the aging process accelerated in chronic obstructive pulmonary disease?Curr Opin Pulm Med2011; 17: 90–97.
29.
YaoHChungSHwangJWRajendrasozhanSSundarIKDeanDAMcBurneyMWGuarenteLGuWRöntyMKinnulaVLRahmanI. SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice. J Clin Invest2012; 122: 2032–45.
30.
BradfuteSBGraubertTAGoodellMA. Roles of Sca-1 in hematopoietic stem/progenitor cell function. Exp Hematol2005; 33: 836–43.
31.
BonyadiMWaldmanSDLiuDAubinJEGrynpasMDStanfordWL. Mesenchymal progenitor self-renewal deficiency leads to age-dependent osteoporosis in Sca-1/Ly-6A null mice. Proc Natl Acad Sci U S A2003; 100: 5840–45.
HeSHeZChenYYeJZongDZhangYChenP. C-Kit/c-Kit ligand interaction of bone marrow endothelial progenitor cells is influenced in a cigarette smoke extract-induced emphysema model. Exp Lung Res2013; 39: 258–67.
34.
ItoKHiraoAAraiFTakuboKMatsuokaSMiyamotoKOhmuraMNakaKHosokawaKIkedaYSudaT. Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med2006; 12: 446–51.
35.
TzortzakiEGPapiANeofytouESoulitzisNSiafakasNM. Immune and genetic mechanisms in COPD: possible targets for therapeutic interventions. Curr Drug Targets2013; 14: 141–8.
36.
Garcia-DominguezPDell'aversanaCAlvarezRAltucciLde LeraAR. Synthetic approaches to DNMT inhibitor SGI-1027 and effects on the U937 leukemia cell line. Bioorg Med Chem Lett2013; 23: 1631–5.
37.
NiehrsC. Active DNA demethylation and DNA repair. Differentiation2009; 77: 1–11.
38.
BaryshnikovaEDestroAInfanteMVCavutoSCariboniUAlloisioMCeresoliGLLutmanRBrambillaGChiesaGRavasiGRoncalliM. Molecular alterations in spontaneous sputum of cancer-free heavy smokers: results from a large screening program. Clin Cancer Res2008; 14: 1913–9.
