Functional characterization of hNUDC as a novel accumulator that specifically acts on in vitro megakaryocytopoiesis and in vivo platelet production.
Human NUDC (hNUDC) has been previously described as a human homolog of a fungal nuclear migration protein. It is a multifunctional interactive protein that forms an association with the microtubule motor complex in a variety of cells. Our recent studies demonstrated that hNUDC could bind specifically to the thrombopoietin receptor (Mpl) and suggest a potential role for hNUDC in megakaryocytopoiesis and thrombopoiesis. The present study is designed to define its biological activity. We demonstrate that the recombinant hNUDC significantly increases megakaryocyte maturation in serum-free liquid-cultured human CD34(+) cells and stimulates colony formation in serum-free semi-solid cultures. Flow cytometry analyses also confirm the stimulatory effect of hNUDC on megakaryocyte polyploidization and in vitro platelet production. In vivo experiments further demonstrate that the administration of hNUDC substantially enhance the number of circulating platelets in normal mice.
Wei
Ming-Xu
MX
State Key Laboratory of Biocontrol, Biotechnology Research Center, Zhongshan University, Guangzhou, The People's Republic of China.
Yang
Yan
Y
Ge
Yi-Chen
YC
Xu
Peilin
P
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D003114:Colony-Forming Units Assay / Q000379:methods; D005434:Flow Cytometry / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology*; D051379:Mice; D008870:Microtubules / Q000502:physiology; D009687:Nuclear Proteins / Q000302:isolation & purification / Q000378:metabolism*; D019007:P-Selectin / Q000032:analysis / Q000737:chemistry; D040201:Platelet Membrane Glycoprotein IIb / Q000032:analysis / Q000737:chemistry; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D034061:Thrombopoiesis / Q000502:physiology*; D013926:Thrombopoietin / Q000378:metabolism*
D018797:Cell Cycle Proteins; C512648:NUDC protein, human; D009687:Nuclear Proteins; C512649:Nudc protein, mouse; D019007:P-Selectin; D040201:Platelet Membrane Glycoprotein IIb; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; C082218:MPL protein, human; D013926:Thrombopoietin