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PDGF Isoforms (pdgf + isoform)
Selected AbstractsEffects of lipopolysaccharide on platelet-derived growth factor isoform and receptor expression in cultured rat common bile duct fibroblasts and cholangiocytesJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2009Tae-Hyeon Kim Abstract Background and Aim:, Little is known about the role of platelet-derived growth factor (PDGF) in biliary fibrosis in the setting of bacterial colonization of the biliary tree. We therefore sought to investigate whether exposure to bacterial lipopolysaccharide (LPS) alters PDGF isoform and receptor expression in cultured rat common bile duct fibroblasts (CBDF) and normal rat cholangiocytes (NRC). Methods:, Collagen content in cells and media was assessed by colorimetric assay and gel electrophoresis. mRNA levels of PDGF-A and -B, and PDGF-Receptors (PDGF-R) , and , were measured by relative quantitative real-time PCR. Protein levels of PDGF-AA, AB and BB were measured by ELISA, and PDGF-R, and PDGF-R, by Western blot. Results:, In CBDF, LPS increased total soluble collagen synthesis and secretion. PDGF-R, and , mRNA and protein were also increased by LPS treatment in CBDF. Lipopolysaccharide treatment elicited an increase in PDGF-A and -B mRNA levels in CBDF. In NRC, levels of PDGF-A mRNA increased in a dose-dependent fashion following LPS treatment, whereas PDGF-B mRNA showed no response. PDGF-AA secretion was higher by CBDF than by NRC. PDGF-BB levels were also higher in CBDF than in NRC. While PDGF-BB levels did not respond to LPS treatment in CBDF, there was a dose-dependent response of this isoform to LPS in NRC. Intracellular and secreted PDGF-AB increased with LPS treatment in NRC. Conclusions:, These results support a model in which chronic bacterial colonization of the biliary tree induces fibrosis through PDGF-dependent mechanisms. [source] Platelet-derived growth factor (PDGF) in human acute myelogenous leukemia: PDGF receptor expression, endogenous PDGF release and responsiveness to exogenous PDGF isoforms by in vitro cultured acute myelogenous leukemia blastsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2001Brynjar Foss Abstract: We investigated effects of Platelet-derived growth factor (PDGF) and Platelet factor 4 (PF-4) on the functional characteristics of native, human acute myelogenous leukemia (AML) blasts. AML blast expression of the PDGF-receptor ,-chain was detected for a subset of patients (45%), whereas PDGF-receptor ,-chain expression was detected for most patients (90%). Constitutive AML blast release of the PDGF-AB isoform (the major form also derived from normal platelets) was detected for 43% of patients, whereas PDGF-BB release was not detected for any patient. The PDGF isoforms AA, AB and BB had dose-dependent and divergent effects on spontaneous and cytokine-dependent AML blast proliferation, whereas for constitutive cytokine secretion (IL-1,, IL-6, TNF-,) inhibitory effects were rare and all three isoforms usually had no effect or enhanced the constitutive secretion. The PDGF effects were caused by a direct effect on the AML blasts and were not dependent on the presence of serum. The PDGF effects could also be detected after in vitro culture of AML cells in the presence of IL-4+granulocyte-macrophage colony stimulating factor. PF-4 had divergent effects on proliferation and cytokine secretion by native AML blasts. Our results suggest that exogenous (e.g. platelet-secreted) PDGF and PF-4 can function as regulators of leukemic hematopoiesis and possibly also modulate the function of residual AML cells in peripheral blood stem cell grafts. On the other hand, endogenous release of PDGF-AB by native blasts may modulate the function of normal cells in the bone marrow microenvironment (e.g. bone marrow stromal cells). [source] To go or not to go: Migration of human mesenchymal progenitor cells stimulated by isoforms of PDGFJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2004Jörg Fiedler Abstract The recruitment of mesenchymal progenitor cells (MPCs) and their subsequent differentiation to osteoblasts is mandatory for bone development, remodeling, and repair. To study the possible involvement of platelet-derived growth factor (PDGF) isoforms, primary human MPCs and osteogenic differentiated progenitor cells (dOB) were examined for chemotaxic response to homodimeric human platelet-derived growth factor AA, -BB, and heterodimeric PDGF-AB. The role of PDGF receptors was addressed by preincubation with PDGF receptor alpha and beta chain specific antibodies. Migration of MPCs, dOB, and primary osteoblasts (OB) was stimulated by the addition of rhPDGF-AA, rhPDGF-BB, and rhPDGF-AB. The effect was highest in MPCs and for rhPDGF-BB, and declining with osteogenic differentiation. Preincubation with the receptor alpha specific antibody decreased the CI to borderline values while pretreatment with the receptor beta specific antibody led to a complete loss of chemotactic response to PDGF isoforms. In control experiments, basal migration values and rhBMP-2 as well as rxBMP-4 induced chemotaxis of MPC were not influenced by the addition of receptor alpha or beta antibodies. Interestingly, without preincubation the parallel exposure of MPC to rhTGF-,1 instantaneously leads to a selective loss of migratory stimulation by rhPDGF-AA. The chemotactic effect of PDGF isoforms for primary human MPCs and the influence of osteogenic differentiation suggest a functional role for recruitment of MPCs during bone development and remodeling. Moreover, these observations may be useful for novel approaches towards guided tissue regeneration or tissue engineering of bone. © 2004 Wiley-Liss, Inc. [source] Different mechanisms influencing permeation of PDGF-AA and PDGF-BB across the blood,brain barrierJOURNAL OF NEUROCHEMISTRY, Issue 1 2003Abba J. Kastin Abstract Platelet-derived growth factor (PDGF) exerts neurotrophic and neuromodulatory effects on the CNS. To determine the permeability of the blood,brain barrier (BBB) to PDGF, we examined the blood-to-brain influx of radioactively labeled PDGF isoforms (PDGF-AA and PDGF-BB) by multiple-time regression analysis after intravenous (i.v.) injection and by in-situ perfusion, and also determined the physicochemical characteristics which affect their permeation across the BBB, including lipophilicity (measured by octanol:buffer partition coefficient), hydrogen bonding (measured by differences in octanol : buffer and isooctane : buffer partition coefficients), serum protein binding (measured by capillary electrophoresis), and stability of PDGF in blood 10 min after i.v. injection (measured by HPLC). After i.v. bolus injection, neither 125I-PDGF-AA nor 125I-PDGF-BB crossed the BBB, their influx rates being similar to that of the vascular marker 99mTc-albumin. 125I-PDGF-AA degraded significantly faster in blood than 125I-PDGF-BB. PDGF-BB, however, was completely bound to a large protein in serum whereas PDGF-AA showed no binding. Thus, degradation might explain the poor blood-to-brain influx of PDGF-AA, whereas protein binding could explain the poor influx of circulating PDGF-BB. Despite their lack of permeation in the intact mouse, both 125I-PDGF-AA and 125I-PDGF-BB entered the brain by perfusion in blood-free buffer, and the significantly faster rate of 125I-PDGF-AA than 125I-PDGF-BB may be explained by the lower hydrogen bonding potential of 125I-PDGF-AA. Thus, the lack of significant distribution of PDGF from blood to brain is not because of the intrinsic barrier function of the BBB but probably because of degradation and protein binding. Information from these studies could be useful in the design of analogues for delivery of PDGF as a therapeutic agent. [source] | |||||||||||||