title: The possible role of ribosomal protein S6 kinase 4 in the senescence of endothelial progenitor cells in diabetes mellitus.
abstract: BACKGROUND
  The decrease and dysfunction of endothelial progenitor cells (EPCs) has been assumed as an important cause/consequence of diabetes mellitus (DM) and its complications, in which the senescence of EPCs induced by hyperglycemia may play an immensurable role. However, the mechanisms of EPCs senescence has not been fully investigated. Recently, ribosomal protein S6 kinase 4 (RSK4), a member of serine/threomine (Ser/Thr) kinase family and p53-related gene, is reported to regulate the replicative and stress-induced senescence of different cells.
  
  
  OBJECTIVE
  These above lead to consideration of an evidence-based hypothesis that RSK4 may serve as a mediator of EPCs senescence in DM.
  
  
  METHODS
  EPCs of healthy subjects and DM patients are isolated from peripheral blood and incubated with high glucose (HG). Then, the EPCs senescence would be detected by senescence associated β-galactosides (SA-β-gal) staining. Meanwhile, the RSK4 expression is assessed by RT-PCR and western blot. Moreover, overexpressing or RNA interfering of RSK4 in EPCs to investigate the relationship between RSK4 expression and the senescence of EPCs are necessary to substantiate this hypothesis. Also, studies on possible upstream and downstream factors of RSK4 would be explored to reveal the RSK4-mediated senescence pathway in EPCs.
  
  
  CONCLUSIONS
  If proved, this hypothesis will provide another mediator of EPCs senescence, and may establish a novel pathogenesis for DM and further benefit to the management of DM.
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yin
authors.forename: Linni
authors.initials: L
authors.lastname: Fan
authors.forename: Gaosheng
authors.initials: G
authors.lastname: Huang
authors.forename: Haichang
authors.initials: H
authors.lastname: Wang
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
mesh_terms: D015153:Blotting, Western; D016022:Case-Control Studies; D002478:Cells, Cultured; D016922:Cellular Senescence; D003920:Diabetes Mellitus / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D042783:Endothelial Cells / Q000201:enzymology* / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D012107:Research Design; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000201:enzymology* / Q000473:pathology; D014162:Transfection; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: C501305:RPS6KA6 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D001616:beta-Galactosidase; D005947:Glucose