Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study the temporal and spatial appearance of aortic cell clusters in bovine embryos is described. Aorta-associated c-kit-positive cell clusters can be observed first in 23 days post inseminationem (dpi) bovine embryos and disappear after 34 dpi. For the first time, it was shown that the immunophenotype of these aortic cluster cells changes during embryonic development. Aortic cell clusters are c-kit+/CD45-/STA-, when they are first detected in the 23 dpi embryo, and acquire a c-kit+/CD45+/STA- phenotype in 27-29 embryos and a c-kit+/CD45+/STA+ immunophenotype in 32-34-day-old specimens. Cell clusters are most prominent in the vicinity of lateral and ventral aortic branches, but rare in omphalomesenteric arteries and absent in Aa. umbilicales. Free c-kit-positive cells in an intravasal position are common, suggesting separation from the clusters in order to colonize subsequent hematopoietic organs, i.e., the liver and the mesonephros. Transmission electron microscopic analysis reveals the existence of primitive desmosomes between the clusters cells and adjacent endothelial cells as well as a fine basal lamina as a demarcation between the cluster cells and underlying mesenchymal cells. Material resembling extracellular matrix is found in large vacuoles in cluster cells of 23 dpi embryos. Immunocytochemistry reveals an intense accumulation of heparan sulfate proteoglycan and collagen IV in the aortic wall at the sites where cell clusters are attached. These observations suggest that the hematopoietic cell clusters induce the formation of a specific microenvironment within the aortic wall.
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PMID:Immunophenotyping and spatio-temporal distribution of aortic cell clusters in the bovine embryo. 1708 23

Thiazolidinediones (TZDs) are insulin-sensitizing agents that also decrease systemic blood pressure, attenuate the formation of atherosclerotic lesions, and block remodeling of injured arterial walls. Recently, TZDs were shown to prevent pulmonary arterial (PA) remodeling in rats treated with monocrotaline. Presently we report studies testing the ability of the TZD rosiglitazone (ROSI) to attenuate pathological arterial remodeling in the lung and prevent the development of pulmonary hypertension (PH) in rats subjected to chronic hypoxia. PA remodeling was reduced in ROSI-treated animals exposed to hypoxia compared with animals exposed to hypoxia alone. ROSI treatment blocked muscularization of distal pulmonary arterioles and reversed remodeling and neomuscularization in lungs of animals previously exposed to chronic hypoxia. Decreased PA remodeling in ROSI-treated animals was associated with decreased smooth muscle cell proliferation, decreased collagen and elastin deposition, and increased matrix metalloproteinase-2 activity in the PA wall. Cells expressing the c-Kit cell surface marker were observed in the PA adventitia of untreated animals exposed to hypoxia but not in ROSI-treated hypoxic rats. Right ventricular hypertrophy and cardiomyocyte hypertrophy were also blunted in ROSI-treated hypoxic animals. Interestingly, mean PA pressures were elevated equally in the untreated and ROSI-treated groups, indicating that ROSI had no effect on the development of PH. However, mean PA pressure was normalized acutely in both groups of hypoxia-exposed animals by Fasudil, an agent that inhibits RhoA/Rho kinase-mediated vasoconstriction. We conclude that ROSI can attenuate and reverse PA remodeling and neomuscularization associated with hypoxic PH. However, this agent fails to block the development of PH, apparently because of its inability to repress sustained Rho kinase-mediated arterial vasoconstriction.
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PMID:Rosiglitazone attenuates hypoxia-induced pulmonary arterial remodeling. 1718 21

BIBF 1000 is a small molecule inhibitor targeting the receptor kinases of platelet-derived growth factor (PDGF), basic fibroblast growth factor and vascular endothelial growth factor, which have known roles in the pathogenesis of pulmonary fibrosis. The anti-fibrotic potential of BIBF 1000 was determined in a rat model of bleomycin-induced lung fibrosis and in an ex vivo fibroblast differentiation assay. Rats exposed to a single intra-tracheal injection of bleomycin were treated with BIBF 1000 starting 10 days after bleomycin administration. To gauge for anti-fibrotic activity, collagen deposition and pro-fibrotic growth factor gene expression was analysed in isolated lungs. Furthermore, the activity of BIBF 1000 was compared with imatinib mesylate (combined PDGF receptor, c-kit and c-abl kinase inhibitor) and SB-431542 (transforming growth factor (TGF)-beta receptor I kinase inhibitor) in an ex vivo TGF-beta-driven fibroblast to myofibroblast differentiation assay, performed in primary human bronchial fibroblasts. Treatment of rats with BIBF 1000 resulted in the attenuation of fibrosis as assessed by the reduction of collagen deposition and the inhibition of pro-fibrotic gene expression. In the cellular assay both SB-431542 and BIBF 1000 showed dose-dependent inhibition of TGF-beta-induced differentiation, whereas imatinib mesylate was inactive. BIBF 1000, or related small molecules with a similar kinase inhibition profile, may represent a novel therapeutic approach for the treatment of idiopathic pulmonary fibrosis.
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PMID:Inhibition of PDGF, VEGF and FGF signalling attenuates fibrosis. 1730 Oct 95

We have shown previously that neonatal testicular gonocytes express platelet-derived growth factor receptors (PDGFR) alpha and beta. We report the expression of a novel PDGFRbeta (V1-PDGFRbeta) transcript in gonocytes of 3-d-old rat testes. V1-PDGFRbeta nucleotide sequence spans from intron 6 to exon 23 of the PDGFRbeta gene, and is predicted to encode a protein lacking part of the extracellular domain. V1-PDGFRbeta transcripts are expressed preferentially in developing gonads. The embryonic teratocarcinoma F9 cells, in which differentiation is driven by retinoic acid (RA), express V1-PDGFRbeta, but not wild-type PDGFRbeta. Green fluorescent protein-tagged V1-PDGFRbeta localized mainly in cytosol of F9, MA-10, and COS-1 cells. FLAG and green fluorescent protein-tagged V1-PDGFRbeta displayed tyrosine kinase activities and contain phosphotyrosine residues, suggesting that V1-PDGFRbeta is a cytosolic tyrosine kinase. Treatment of F9 cells with RA induced V1-PDGFRbeta gene expression, concomitant with changes in morphology and increased mRNA expression of collagen IV and laminin B1, suggesting that V1-PFGRbeta is involved in cell differentiation. Similarly, treatment of postnatal d 3 rat gonocytes with RA induced a dose-dependent increase in V1-PDGFRbeta expression together with an increase in c-kit and Stra8, markers of more differentiated germ cells and a concomitant decrease in GFRalpha1, a marker of spermatogonial stem cells. However, an excess of V1-PDGFRbeta inhibited RA-mediated collagen IV and laminin B1 expression and altered both RA-dependent and RA-independent morphological changes in F9 cells, while increasing cell survival. These results suggest that the expression of V1-PDGFRbeta is tightly regulated during differentiation and that it may play an active role in germ cell differentiation.
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PMID:Identification and distribution of a novel platelet-derived growth factor receptor beta variant: effect of retinoic acid and involvement in cell differentiation. 1730 70

The rhythmic motility of the intestine is regulated by the interstitial cells of Cajal (ICC) and the enteric nervous system. Rhythmic motility is considered to occur after the differentiation of mesenchymal progenitor cells into ICC during the late embryonic period. In this study, we successfully reconstructed a gut-like tissue demonstrating rhythmic contractions by culturing dispersed cells enzymatically isolated from the mouse intestine during the mid-embryonic period. These intestinal cells were reconstituted into a collagen gel at high density, made to proliferate considerably, and grew into a gut-like tissue after 1 week of culturing. The reconstituted tissue showed rhythmic contractions and stained positive for the specific marker proteins of neurones and ICC, PGP9.5 and c-Kit. The tissue also demonstrated network formation by developing nerve cells and ICC. Moreover, in the presence of nifedipine, c-Kit-immunopositive cells showed spontaneous Ca(2+) oscillation, which is considered to be coupled to the electrical activity that corresponds to slow waves. Therefore, this culture system may be of use in elucidating the developmental mechanisms of gastrointestinal motility.
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PMID:In vitro development of gut-like tissue demonstrating rhythmic contractions from embryonic mouse intestinal cells. 1739 Dec 45

Penile malignancies are rare in developed countries. The authors present a case of a penile urethral mesenchymal tumor occurring in a 51-year-old Caucasian male and displaying light microscopic, immunohistochemical, and ultrastructural features suggestive of a pacemaker cell type, combined with a lack of diagnostic features of any other established tumor category. The immunohistochemical profile was intensely positive for vimentin, PKC theta, and NSE and weakly positive to nonreactive for CD34 and smooth muscle actin, and entirely negative for CD117 (c-kit), S-100, and other markers. C-kit and PDGFRA gene analysis showed no mutations. Electron microscopy revealed tumor cells with plentiful cytoplasm and cytoplasmic processes/filopodia, both filled with intermediate filaments and occasional solitary focal densities. There were also prominent smooth endoplasmic reticulum cisternae, caveolae, neurosecretory granules, particularly concentrated in cytoplasmic processes, and synaptic-type structures. Poorly formed basal lamina, gap junctions, and intercellular collagen aggregates, consistent with skeinoid-type fibers, were also noted. Interstitial cells with potential pacemaker function have been recently described in the lower urinary tract, including the urethra, and this tumor may be related to this cellular phenotype.
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PMID:Urethral stromal tumor with pacemaker cell phenotype. 1745 99

Solitary fibrous tumor (SFT) is an unusual mesenchymal neoplasm that most often arises in the pleura; however, it has recently been described in a number of extrapleural sites. This report describes an extremely rare case of a benign SFT arising in the pancreas. A 41-year-old woman presented in the clinic with right upper abdominal pain. Subsequent ultrasonographic studies revealed a 1.5x1.5x1.4 cm hypoechoic mass within the pancreatic body, which was later confirmed on both helical computerized tomography and magnetic resonance imaging studies. An endocrine tumor was clinically suspected. Laparoscopic enucleation of the mass was performed. Microscopically, the tumor was composed of bland uniform spindle cells arranged between collagen bundles. On immunohistochemical studies, these spindle cells were positive for CD34 and bcl-2 but negative for cytokeratin (AE1+AE3 and Cam5.2), smooth muscle actin, desmin, S-100, and c-kit. Based on the light microscopic morphology and immunohistochemical staining profile, the diagnosis of SFT was rendered.
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PMID:Solitary fibrous tumor of the pancreas: a case report. 1765 47

Rheumatoid arthritis (RA) is a chronic inflammatory disease that is associated with joint destruction. Imatinib mesylate (imatinib) is an inhibitor that specifically targets a set of protein tyrosine kinase, such as abl, c-kit, and platelet-derived growth factor receptor (PDGFR) and it is widely used to treat chronic myeloid leukemia (CML). The purpose of the present study is to determine whether imatinib can provide benefit in the arthritis induced by anti-collagen type II antibody (CAIA) in mice, a model that provides an opportunity to study the effector inflammatory phase of arthritis without involving the priming phase of the immune responses. Mice treated with intraperitoneal administration of imatinib (1 or 10 mg/kg) prior to the development of CAIA displayed significant reductions in the severity of CAIA as assessed by arthritis score, histology, and synovial PDGF and vascular endothelial growth factor expression. In addition, treatment of the mice that had developed CAIA with intraperitoneal administration of imatinib (1 or 10 mg/kg) inhibited the progression of arthritis as assessed by those parameters. These results suggest that imatinib prevents and treats CAIA. Imatinib may thus have both a preventive and therapeutic potential for the joint inflammation at the effector stage of RA.
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PMID:Imatinib mesylate both prevents and treats the arthritis induced by type II collagen antibody in mice. 1769 64

Profibrogeneic cytokines contribute to the accumulation of myofibroblasts in the lung interstitium in idiopathic pulmonary fibrosis (IPF). Imatinib mesylate, a tyrosine kinase inhibitor specific for Abl, platelet-derived growth factor receptor (PDGFR) and c-Kit tyrosine kinases, has been shown to inhibit fibrosis and profibrotic signaling in mouse models of inflammation-mediated lung reactions. The authors tested imatinib mesylate in vivo in a mouse model of crocidolite asbestos-induced progressive fibrosis. The ability of imatinib mesylate to inhibit profibrogeneic cytokine-induced human pulmonary fibroblast migration was tested in vitro and the expression of its target protein tyrosine kinases was assessed with immunofluorescence. In vivo, 10 mg/kg/day imatinib mesylate inhibited histological parenchymal fibrosis and led to a decrease in collagen deposition, but had no significant effect on asbestos-induced neutrophilia. However, 50 mg/kg/day imatinib mesylate did not inhibit collagen deposition. In vitro, IPF fibroblasts expressed Abl, PDGFR-alpha, PDGF-beta, but not c-Kit, and 1 microM imatinib mesylate inhibited profibrogeneic cytokine-induced IPF fibroblast migration. These results suggest that imatinib mesylate is a potential and specific inhibitor of fibroblast accumulation in asbestos-induced pulmonary fibrosis.
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PMID:Imatinib mesylate inhibits fibrogenesis in asbestos-induced interstitial pneumonia. 1784 62

Hepatic stellate cells are believed to play a key role in the development of liver fibrosis. Several studies have reported that bone marrow cells can give rise to hepatic stellate cells. We hypothesized that hepatic stellate cells are derived from hematopoietic stem cells. To test this hypothesis, we generated chimeric mice by transplantation of clonal populations of cells derived from single enhanced green fluorescent protein (EGFP)-marked Lin(-)Sca-1(+)c-kit(+)CD34(-) cells and examined the histology of liver tissues obtained from the chimeric mice with carbon tetrachloride (CCl(4))-induced injury. After 12 weeks of CCl(4) treatment, we detected EGFP(+) cells in the liver, and some cells contained intracytoplasmic lipid droplets. Immunofluorescence analysis demonstrated that 50% to 60% of the EGFP(+) cells were negative for CD45 and positive for vimentin, glial fibrillary acidic protein, ADAMTS13, and alpha-smooth muscle actin. Moreover, EGFP(+) cells isolated from the liver synthesized collagen I in culture. These phenotypes were consistent with those of hepatic stellate cells. The hematopoietic stem cell-derived hepatic stellate cells seen in male-to-male transplants revealed only one Y chromosome. Our findings suggest that hematopoietic stem cells contribute to the generation of hepatic stellate cells after liver injury and that the process does not involve cell fusion.
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PMID:Hematopoietic origin of hepatic stellate cells in the adult liver. 1804 97


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