Soluble osteopontin inhibits apoptosis of adherent endothelial cells deprived of growth factors.
Osteopontin (OPN) is primarily an extracellular glycosylated phosphoprotein capable of stimulating cell migration and cell attachment, predominantly to mineralized surfaces. Found in moderate levels in plasma, it acts as a cytokine able to modify gene expression via integrins and certain CD44 isoforms. In this work we show that soluble OPN inhibits apoptosis of adherent human umbilical vein endothelial cells incubated in medium lacking critical growth factors and cytokines. In a dose-dependent manner OPN reduced the formation of apoptotic bodies and suppressed DNA fragmentation. OPN also caused an increase in Bcl-X(L) mRNA levels, suppressed the apparent dispersion of Bcl-X(L) throughout the cytoplasm, and slightly enhanced IkappaB-alpha protein degradation. These data suggest that a function of OPN in homeostatic processes is to facilitate the survival of stressed endothelial cells, possibly by occupying unligated integrins and suppressing integrin-mediated death.
Khan
S A
SA
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey 08854, USA.
Lopez-Chua
C A
CA
Zhang
J
J
Fisher
L W
LW
Sørensen
E S
ES
Denhardt
D T
DT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002417:Cattle; D002478:Cells, Cultured; D003470:Culture Media; D004268:DNA-Binding Proteins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006133:Growth Substances; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D020672:I-kappa B Proteins; D016023:Integrins / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D053495:Osteopontin; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology*; D012995:Solubility; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D003470:Culture Media; D004268:DNA-Binding Proteins; D006133:Growth Substances; D018960:Hyaluronan Receptors; D020672:I-kappa B Proteins; D016023:Integrins; C000606204:NFKBIA protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011994:Recombinant Proteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D051020:bcl-X Protein; D053495:Osteopontin; D000072000:NF-KappaB Inhibitor alpha