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At least 1,189 records · Page 66Linked to original sources
PubMed1999

[Different expressions of cyclins and cyclin dependent kinase inhibitor P27 in vascular smooth muscle cells and cardiac myocytes caused by angiotensin II and PDGF stimulation].

OBJECTIVE: To investigate cell cycle distribution of the vascular smooth muscle cells (VSMC) and cardiac myocytes(CM) and different expressions of cyclins and P27 caused by angiotensin II (Ang II) and platelet derived growth factor BB (PDGF-BB). METHODS: Cultured VSMCs or CMs were collected at 24 h after stimulation of Ang II (10(-6) mol/L) and PDGF-BB (20 ng/ml). Cell cycle distribution, cyclins and P27 expression were determined with flow cytometer. RESULTS: Ang II had no effect on P27 expression in both VSMCs and CMs. It did not cause proliferation of both VSMCs and CMs. Although PDGF-BB could significantly increase cyclins expression in both VSMCs and CMs, it could only significantly inhibit P27 expression in VSMCs (1.8 +/- 1.3 vs 48.1 +/- 5.4, P < 0.01) and cause VSMC proliferation, and had no effect on P27 expression in CMs(39.4 +/- 5.6 vs 44.6 +/- 3.6, P > 0.05). CONCLUSION: The progression of VSMC and CM through G1 to S phase might be brought out by the inhibition of P27 during proliferation.

Angiotensin II↗
PubMed2000

[Research progress of fibroblast and wound repair].

OBJECTIVE: To review the recent advances in fibroblast study and its role in wound repair. METHODS: Recent original articles related to wound repair were retrieved extensively, and the effect of fibroblast on every stages of repair were summed up and comprehended. RESULTS: Fibroblast plays important roles in granulation formation, wound contraction, matrix synthesis, wound repair, scar formation and scarless repair by means of growth factors modulation. CONCLUSION: The understanding of fibroblast in the wound repair can promote the progress of biological therapy of wound repair and scar prevention.

Animals↗
PubMed2001

[The biological function of platelet-derived growth factor-BB in the osteoblast-osteoclast co-culture system].

OBJECTIVE: To investigate the biological effects of platelet-derived growth factor (PDGF)-BB on the osteoclasts in the osteoblast-osteoclast co-culture system. METHODS: The human osteoblasts and osteoclasts were isolated from the iliac crest of patients and co-cultured in the same system. The PDGF-BB or PDGF-BB + NO synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA) was administered to the co-culture system. The tartrate-resistant acid phosphatase (TRAP) activities in the medium were measured by enzyme kinetics. The resorption pits were stained by toludine blue. The area and number of the resorption pits were determined with the Leica Quantimet 500 system. RESULTS: Under the stimuli of PDGF-BB in the co-culture system, TRAP activities changed from 1.40 U/L +/- 0.12 U/L to 1.46 U/L +/- 0.08 U/L (P > 0.05) in the medium, and the area and number of resorption pits was changed from (427 +/- 149) micrometer(2) and (13.3 +/- 0.9) per slice to (436 +/- 147) micrometer(2) and (14.1 +/- 1.2) per slice respectively (P > 0.05). After the L-NMMA was applied to the system, the TRAP activities rose significantly from 1.46 U/L +/- 0.10 U/L to 2.47 U/L +/- 0.38 U/L along with the increase of dose of PDGF-BB, and the number and area of the resorption pits increased significantly from 436 micrometer(2) +/- 147 micrometer(2) and (14.1 +/- 1.2) per slice to 592 micrometer(2) +/- 171 micrometer(2) and (22.5 +/- 1.7) per slice. Both the TRAP activities and resorption pits rose significantly after the L-NMMA was administered. Comparisons of different treatment groups were made using analysis of variance (ANOVA) with multiple comparisons and a Student-Newman-Keuls test. CONCLUSIONS: The nitric oxide (NO) was produced by osteoblasts stimulated by PDGF-BB in the osteoblast-osteoclast co-culture system. Therefore, the direct promotion effects of PDGF-BB on the osteoclasts were inhibited.

Acid Phosphatase↗
PubMed2001

[The role of cyclin-dependent kinase inhibitors in hyperplasia and hypertrophy of vascular smooth muscle cells].

OBJECTIVE: To investigate the role p27, p21, and p57, different cyclin-dependent kinase inhibitors (CKIs), play in the hyperplasia and hypertrophy of vascular smooth muscle cells (VSMCs) stimulated with platelet-derived growth factor (PDGF-BB) and angiotensin II (Ang II). METHODS: VSMCs from rat aorta were cultured. PDGF-BB and Ang II were added into the serum-free media at the concentrations of 10 - 6 M and 20 ng/ml respectively. VSMCs were harvested after 6h, 12h, and 24 h or stimulation. The protein levels of p27, p21 and p57 in VSMCs were examined with Western blot analysis. RESULTS: The protein levels of p27, p21, and p57 in the Ang II-stimulated VSMCs were similar to those in the quiescent cells (P > 0.05). The protein levels of p21 and p57 in the PDGF-BB-stimulated VSMCs increased along with the time course of stimulation, the former being at its peak value at the 24th hour, and were significantly higher than those in Ang II-stimulated VSMCs. However, the p57 protein level was high in the quiescent cells. A remarkable decrease of the p57 protein level was found in the PDGF-BB-stimulated VSMCs (P < 0.01). CONCLUSION: p27, p21, and p57 proteins play important roles in regulating hyperplasia and hypertrophy of VSMC. P21 and p57 prevent the overplasia of VSMCs. P27 is the most important regulator of hyperplasia and hypertrophy of VSMC stimulated by PDGF and Ang II.

Angiotensin II↗
PubMed1999

[The potential role of cytokines expression in idiopathic pulmonary fibrosis].

OBJECTIVE: To investigate the protein and gene expression in bronchoalveolar lavage cells and open lung biopsies from patients with IPF. METHODS: The immunohistochemical methods were used to analyze the expression of PDGF, TGF-beta in bronchoalveolar lavage cells of patients with IPF. For open lung biopsies, both immunohistochemistry and in situ hybridization were used. RESULTS: In specimens of bronchoalveolar lavage fluid, PDGF-AA, PDGF-BB, TGF-beta were localized to alveolar macrophages in patients with IPF. Though there were no differences between IPF and sarcoidosis in terms of the staining intensity (2.5 - 3.0) or number of positive cells 81% - 90%, the number of such cells were less in the control (0 - 1.7, 25% - 32% respectively). Evaluation of open lung biopsies from patients with IPF showed that PDGF, TGF-beta proteins were localized to hyperplastic bronchio-alveolar epithelial cells (2.4 - 3.7, in control 0), alveolar macrophages (2.9 - 3.7, in control 0.8 - 1.3), fibroblasts (3.0 - 3.6, in control 2.7 - 2.8), vascular smooth muscle cells, vascular endothelial cells, and fibroblast-like cells surrounding pulmonary vessels (2.7 - 4.0, in control 2.1 - 2.9). In situ hybridization results were consistent with that of immunohistochemistry except that PDGF and TGF-beta mRNA transcripts were not detected in bronchio-alveolar epithelial cells. In control lungs, however, both ISH and IHC revealed that PDGF and TGF-beta were only present in the pleura and in fibroblast-like cells surrounding pulmonary vessels. CONCLUSIONS: PDGF and TGF-beta, which interplay with pulmonary mesenchymal cells, are involved in fibroplasia and deposition of extracellular matrix as well as angiogenesis and epithelial cell repopularization.

Becaplermin↗
PubMed2001

[Gene therapy in diabetic foot].

In gene therapy nucleic acids are used for therapy. There are three different concepts in gene therapy for chronic wounds. (1) Synthesis of human recombinant growth factors by gene therapy techniques, (2) Ex-vivo transfection of cell cultures (fibroblasts, keratinocytes) with growth factor DNA and subsequent transplantation of transfected cells on chronic wounds. (3) In-vivo transfection with growth factor DNA, e.g., gene gun, liposomes, viral vector. Clinical studies on gene therapy for diabetic foot ulcers are only available for the local application of human recombinant PDGF-BB growth factor. Meta-analysis shows there is a low but significant effect of PDGF-BB on neuropathic diabetic ulcers, leading to an increase of healing by 10-15% within 20 weeks of treatment.

Animals↗
PubMed2002

Tumor-derived platelet-derived growth factor-BB plays a critical role in osteosclerotic bone metastasis in an animal model of human breast cancer.

Breast cancer produces a variety of growth factors to promote its behavior at primary and secondary sites in autocrine/paracrine manners. However, the role of these growth factors in the colonization of cancer cells in bone, which is one of the most common metastatic sites, is poorly understood. To study this, we established an in vivo model in which the MCF-7 human breast cancer cells caused predominant osteosclerotic bone metastases 20-25 weeks after inoculation into the left cardiac ventricle in female nude mice. To make this model more time efficient, we overexpressed the oncogene Neu, which is associated with aggressive behavior in human breast cancers, in MCF-7 cells (MCF-7/Neu). MCF-7/Neu cells grew without estrogen and developed osteosclerotic bone metastases in 10-12 weeks in animals. Of note, MCF-7/Neu-bearing mice showed substantial plasma levels of human platelet-derived growth factor-BB (hPDGF-BB; 855 +/- 347 pg/ml; mean +/- SE, n = 5), indicating hPDGF-BB production by inoculated MCF-7/Neu cells. MCF-7/Neu cells in culture also produced large amounts of hPDGF-BB. Conditioned medium harvested from MCF-7/Neu cells stimulated osteoblastic bone formation in organ cultures of neonatal mouse calvariae, and a neutralizing antibody to hPDGF-BB blocked the osteoblastic bone formation. Stable transfection of the hPDGF-B AS in MCF-7/Neu cells reduced hPDGF-BB production in culture. Mice bearing these MCF-7/Neu cells with antisense showed reduced bone metastases with decreased plasma hPDGF-BB levels (54 +/- 20 and 35 +/- 21 in two different antisense and 696 +/- 312 pg/ml in empty vector; mean +/- SE; n = 5). Introduction of hPDGF-B cDNA in the MDA-MB-231 human breast cancer cells, which consistently formed osteolytic bone metastases, induced osteosclerotic lesions in the osteolytic bone metastases. In conclusion, we show that MCF-7 cells cause osteosclerotic bone metastases and that Neu enhances this capacity of MCF-7 cells. Our data suggest that MCF-7/Neu-derived hPDGF-BB plays a causative role in the development of osteosclerotic bone metastases in this model.

Animals↗
PubMed2000

[Mechanism of abnormal scars with treatment of steroid].

OBJECTIVE: To investigate the mechanism of steroid in treatment of abnormal scars. METHODS: Apoptosis of different fibroblasts from 6 samples with keloid, 6 samples with hypertrophic scar, and 6 samples of normal skin was observed under the condition of the media containing steroid in vitro. Proliferation, biosynthesis and apoptosis of fibroblasts of 6 samples of hypertrophic scars treated with intralesional injection of steroid were studied in vivo. RESULTS: Steroid could induce apoptosis of different fibroblasts in vitro in correspondence with increasing ratio of Bax/Bcl-2 proteins. Intralesional injection of steroid could inhibit proliferation of fibroblasts from hypertrophic scars by inhibiting PDGF-BB gene expression in vivo. Intralesional injection of steroid could inhibit procollagen gene expression to prohibit type I and III protein syntheses of fibroblasts from hypertrophic scars in vivo by inhibiting gene transcription. Intralesional injection of steroid could increase c-myc and p53 gene expression of hypertrophic scars in vivo, which induced apoptosis of cells. CONCLUSION: The effects of steroid on abnormal scars were achieved by inhibiting proliferation and biosyntheses of fibroblasts and promoting apoptosis of fibroblasts.

Adolescent↗
PubMed2002

The antimitogenic action of the sulphated polysaccharide fucoidan differs from heparin in human vascular smooth muscle cells.

The sulphated polysaccharides fucoidan and heparin both inhibit vascular smooth muscle cell (VSMC) proliferation. In this study we compared their actions on mitogenesis and ERK1/ERK2 activation in human VSMC. Although they displaced cell surface [3H]-heparin binding with similar affinity, they exerted clearly distinguishable actions. Fucoidan potently inhibited DNA synthesis stimulated by foetal calf serum, PDGF-BB and thrombospondin-1. Heparin inhibited the mitogenic action of serum and thrombospondin- I (though less potently than fucoidan), but failed to inhibit PDGF-BB-induced DNA synthesis. In parallel studies, fucoidan, but not heparin, inhibited ERK1/ERK2 activation by PDGF-BB. Moreover, fucoidan inhibited serum-induced mitogenesis in "heparin resistant" VSMC, which are refractory to heparin's antimitogenic action. In summary, the structurally different polysaccharides, heparin, fucoidan (and fucans) have distinguishable effects on mitogenesis and ERK1/ERK2 activation, suggesting that different mechanism(s) mediate these actions. The potent antimitogenic action of fucoidan and its efficacy in heparin resistant VSMC emphasise the need to further investigate its mechanism of action in human VSMC and suggest this agent could have therapeutic potential.

Animals↗
PubMed2002

Macrophage lipoprotein lipase expression is increased in patients with heterozygous familial hypercholesterolemia.

FH is associated with accelerated atherosclerosis. Based on the crucial role of macrophage LPL in atherogenesis, we determined in the present study macrophage LPL expression in patients with FH. Monocytes isolated from 13 FH patients and 13 control subjects were differentiated into macrophages by culturing the cells for 9 days in 20% autologous or heterologous serum. Macrophages of patients with FH cultured in their own sera showed a significant increase in LPL mRNA levels, extracellular LPL mass, and activity compared with macrophages of control subjects. Although these alterations positively correlated with the levels of serum platelet-derived growth factor-BB (PDGF-BB) in FH subjects, increased LPL secretion by cultured FH macrophages was reduced neither by immunoneutralizing FH serum with an anti-PDGF-BB antibody, nor by culturing these cells in sera from control subjects. With the exception of LPL, levels of other cytokines and 8-isoprostane were not increased in the supernatants of macrophages of FH patients. Serum from FH patients also enhances the levels of LPL secreted by macrophages from control subjects. Immunoneutralization of FH serum with an anti-PDGF-BB antibody totally reversed this alteration. Overall, this study demonstrates that macrophages from FH subjects overproduce LPL and that PDGF present in the serum from FH patients stimulates LPL secretion by control macrophages. These findings suggest that macrophage LPL induction in patients with FH might be related to the increased atherogenesis observed in these subjects.

Anticoagulants↗
PubMed1999

[Observations on expression of c-fos and c-myc genes and activity of PDGFBB autocrine loop in 67 human gliomas].

OBJECTIVE: To investigate the variance of expression of c-fos and c-myc genes and the activity of platelet-derived growth factor (PDGF) BB autocrine loop in human gliomas as well as their relationship. METHODS: In situ hybridization and immunohistochemistry were used to study 67 human glioma specimens of different grades. RESULTS: The incidences, of positive expression for c-fos mRNA, c-fos protein, c-myc mRNA and c-myc protein were 100% (67/67), 100% (67/67), 85.1% (57/67) and 83.6% (56/67) respectively. There was significant positive correlation between the positive cell densities of c-fos mRNA (92.49 +/- 33.87) and c-fos protein (91.64 +/- 38.11), and of c-myc mRNA (72.70 +/- 40.56) and c-myc protein (71.49 +/- 41.11, r = 0.917 - 0.988, P < 0.001). All of them also increased correspondingly with the malignant degree of the tumors and level of PDGFB mRNA expression in the tumor cells (P < 0.05 - 0.01). Not only were the positive cell densities of PDGF alpha receptor (58.46 +/- 28.77), PDGF beta receptor (63.03 +/- 31.63) and phosphotyrosine protein (68.25 +/- 29.30) correlated positively with one another (r = 0.827 - 0.896, P < 0.001), but they also all correlated positively with the positive cell densities of PDGFB mRNA, c-fos mRNA, c-fos protein, c-myc mRNA and c-myc protein respectively (r = 0.615 - 0.888, P < 0.001). CONCLUSIONS: The abnormally increased activity of the PDGFBB autocrine loop possibly upregulated the overexpression of c-fos and c-myc genes in glioma cells and suggested that c-fos and c-myc proteins probably played an important role as downstream response factors in the signaling pathway in which PDGFBB could induce gliocyte transformation and glioma development.

Adolescent↗
PubMed2002

Cooperative interaction of Ig(alpha) and Ig(beta) of the BCR regulates the kinetics and specificity of antigen targeting.

Following the binding of antigens, the BCR transduces signals and internalizes antigens for processing and presentation, both of which are required for initiating an effective antibody response. The BCR, consisting of membrane Ig and Ig(alpha)/Ig(beta) heterodimer, facilitates antigen processing by accelerating antigen targeting to the processing compartment. Previous reports showed that Ig(alpha) or Ig(beta) alone is competent for internalizing antigens. However, both Ig(alpha) and Ig(beta) are required for BCR-enhanced antigen presentation. Using chimeric proteins containing the extracellular and transmembrane domains of human platelet-derived growth factor receptor fused with the cytoplasmic domain of Ig(alpha) or Ig(beta), we studied the roles of the cytoplasmic tails of Ig(alpha) and Ig(beta) in BCR-mediated antigen transport. The Ig(beta) chimera rapidly moves through the endocytic pathway to lysosomes, while the Ig(alpha) chimera slows down this movement. The Ig(alpha), but not the Ig(beta) chimera, is required for an increase in the turnover rate of the chimeras in response to stimulation. Only when Ig(alpha) and Ig(beta) chimeras are co-expressed do the chimeras rapidly and specifically target antigens to the processing compartment. These findings suggest that Ig(alpha) and Ig(beta) play distinct roles in BCR trafficking, and the cooperative interaction of Ig(alpha) and Ig(beta) controls and regulates the kinetics and specificity of antigen targeting.

Animals↗
PubMed1998

[Study on relationship of the expression of platelet-derived growth factor and its receptor-beta in liver tissues with liver fibrosis].

The expression of platelet-derived growth factor(PDGF)-BB and PDGF receptor-beta(PDGFR-beta) in liver tissues from viral hepatitis was detected by immunohistochemistry. The results showed that the expression of PDGF-BB and PDGFR-beta in the liver tissues correlated closely with the degree of liver fibrosis. The levels of their expression in the liver cirrhosis and fibrosis stage S3-4 of chronic viral hepatitis(CH) were much higher than those in acute viral hepatitis and fibrosis stage S0-2 of CH. Meanwhile, the expression of PDGF and its receptor was associated with the expression of desmin-positive cells pro-collagen III peptide in liver tissues and tissue inhibitor of metalloprotenase-1 in serum. It is suggested that PDGF-BB and its receptor-beta may promote the progress of liver fibrosis by means of the activation, proliferation and differentiation of satellite cells.

Adult↗
PubMed2002

Origin of coronary endothelial cells from epicardial mesothelium in avian embryos.

It has been established that coronary vessels develop through self-assembly of mesenchymal vascular progenitors in the subepicardium. Mesenchymal precursors of vascular smooth muscle cells and fibroblasts are known to originate from an epithelial-to-mesenchymal transformation of the epicardial mesothelium, but the origin of the coronary endothelium is still obscure. We herein report that at least part of the population of the precursors of the coronary endothelium are epicardially-derived cells (EPDCs). We have performed an EPDC lineage study through retroviral and fluorescent labelling of the proepicardial and epicardial mesothelium of avian embryos. In all the experiments onlythe surface mesothelium was labelled after 3 h of reincubation. However, endothelial cells from subepicardial vessels were labelled after 24-48 h and endothelial cells of intramyocardial vessels were also labelled after 48-96 h of reincubation. In addition, the development of the coronary vessels was studied in quail-chick chimeras, obtaining results which also support a mesothelial origin for endothelial and smooth muscle cells. Finally, quail proepicardial explants cultured on Matrigel showed colocalization of cytokeratin and QH1 (mesothelial and endothelial markers, respectively) after 24 h. These results, taken together, suggest that EPDC show similar competence to that displayed by bipotential vascular progenitor cells [Yamashita et al., Nature 408: 92-96 (2000)] which are able to differentiate into endothelium or smooth muscle depending on their exposure to VEGF or PDGF-BB. It is conceivable that the earliest EPDC differentiate into endothelial cells in response to myocardially-secreted VEGF, while further EPDC would be recruited by the nascent capillaries via PDGFR-beta signalling, giving rise to mural cells.

Animals↗
PubMed2002

The effect of epidermal growth factor & platelet-derived growth factors on wound healing process.

BACKGROUND & OBJECTIVES: Various growth factors play significant roles during the process of wound healing. A systematic study was carried out to evaluate the effects of topically applied epidermal growth factor (EGF) and platelet-derived growth factors (PDGF-BB, PDGF-AB, PDGF-AA) in various concentrations on wound healing. Various combinations of these growth factors were also studied to find the best combination for wound healing. METHODS: Wounds were created on a mouse model. Various concentrations and combinations of EGF and PDGFs were applied topically and the effects on wound healing were monitored visually. RESULTS: EGF, PDGF-AB and PDGF-BB when applied alone or in combination, healed the wounds in significantly less time and with less scar tissue formation compared to the controls. The best results were obtained with a combination of EGF (10 ng) and PDGF-BB (15 ng). PDGF-AA even at the maximum concentration of 20 ng did not enhance the wound repair process. A combination of PDGF-AA (20 ng) with EGF (10 ng) did not enhance the wound repair process either. INTERPRETATION & CONCLUSION: Topically applied EGF, PDGF-AB and PDGF-BB enhanced the wound repair process and had a role in decreasing the formation of scar tissue. PDGF-AA either alone or in combination with EGF did not enhance the wound repair process significantly. It appears that PDGF-AA might be limiting the EGF-mediated wound repair and such observation has not been previously reported in studies on wound healing using topically applied growth factors.

Animals↗