ABSTRACT
OBJECTIVES@#To study the role and mechanism of platelet-derived growth factor BB (PDGF-BB) on platelet production in Kawasaki disease (KD) mice and human megakaryocytic Dami cells through in vitro and invivo experiments.@*METHODS@#ELISA was used to measure the expression of PDGF in the serum of 40 children with KD and 40 healthy children. C57BL/6 mice were used to establish a model of KD and were then randomly divided into a normal group, a KD group, and an imatinib group (30 mice in each group). Routine blood test was performed for each group, and the expression of PDGF-BB, megakaryocyte colony forming unit (CFU-MK), and the megakaryocyte marker CD41 were measured. CCK-8, flow cytometry, quantitative real-time PCR, and Western blot were used to analyze the role and mechanism of PDGF-BB in platelet production in Dami cells.@*RESULTS@#PDGF-BB was highly expressed in the serum of KD children (P<0.001). The KD group had a higher expression level of PDGF-BB in serum (P<0.05) and significant increases in the expression of CFU-MK and CD41 (P<0.001), and the imatinib group had significant reductions in the expression of CFU-MK and CD41 (P<0.001). In vitro experiments showed that PDGF-BB promoted Dami cell proliferation, platelet production, mRNA expression of PDGFR-β, and protein expression of p-Akt (P<0.05). Compared with the PDGF-BB group, the combination group (PDGF-BB 25 ng/mL + imatinib 20 μmol/L) had significantly lower levels of platelet production, mRNA expression of PDGFR-β, and protein expression of p-Akt (P<0.05).@*CONCLUSIONS@#PDGF-BB may promote megakaryocyte proliferation, differentiation, and platelet production by binding to PDGFR-β and activating the PI3K/Akt pathway, and the PDGFR-β inhibitor imatinib can reduce platelet production, which provides a new strategy for the treatment of thrombocytosis in KD.
Subject(s)
Child , Humans , Animals , Mice , Mice, Inbred C57BL , Becaplermin , Imatinib Mesylate/therapeutic use , Mucocutaneous Lymph Node Syndrome/drug therapy , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Thrombocytosis/etiology , RNA, MessengerABSTRACT
<p><b>AIM</b>To explore the influence of simulated altitude hypoxia on dielectric properties of mouse erythrocytes.</p><p><b>METHODS</b>Experimental animals were divided into the plain control group(control) and simulated altitude hypoxia group (altitude). The AC impedance of mouse erythrocytes was measured with the Agilent 4294A impedance analyzer, the influence of simulated altitude hypoxia on dielectric properties of mouse erythrocytes was observed by cell dielectric spectroscopy, Cole-Cole plots, loss factor spectrum, loss tangent spectrum, and curve fitting analysis of Cole-Cole equation.</p><p><b>RESULTS</b>After mice were exposed to hypoxia at simulated 5000 m altitude for 4 weeks, permittivity at low frequency (epsilonl) and dielectric increment (deltaepsilon) increased 57% and 59% than that of control group respectively, conductivity at low frequency (kappal) and conductivity at high frequency (kappah) reduced 49% and 11% than that of control group respectively.</p><p><b>CONCLUSION</b>The simulated altitude hypoxia could arise to increase dielectric capability and depress conductive performance on mouse erythrocytes.</p>