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 leukemic cells, glucose transport is activated by SCF and H2O2 through a common signal cascade involving Akt, PLCgamma, Syk, and the Src family, in this order. An explanation can be provided by the phosphorylation of c-kit, the SCF receptor, elicited by either SCF or H2O2. Moreover, antioxidants prevent the SCF effect on glucose transport, confirming the involvement of H2O2 in the pathway leading to glucose-transport activation and suggesting a potential role for reactive oxygen species in leukemia proliferation.
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PMID:Glucose-transport regulation in leukemic cells: how can H2O2 mimic stem cell factor effects? 1711 33

Tissue stem cells participate in the repopulation of tissue after injury. Tissue injury stimulates the normally quiescent tissue stem cells to differentiate and proliferate, in the process of replacing and/or repairing the damaged cells, and hence effecting tissue regeneration. The salivary glands retain the ability for frequent regeneration. Previously, we isolated progenitor cells from the injured salivary glands of mice and rats that differentiated into hepatic and pancreatic lineages. The isolated progenitors were CD49f-positive and intracellular laminin-positive, and proliferated on type I collagen while maintaining their multipotency. In this study, we analyzed the tissue stem cells induced by ligating the main excretory duct of the salivary gland in swine. After duct ligation of the gland, acinar cells receded due to apoptosis, and epithelial cells subsequently proliferated. We cultured cells obtained from the duct-ligated salivary gland and purified the cells by limited dilution. The isolated cells were positive for CD29, CD49f, intracellular laminin, AFP, CK19, CK18, and Thy-1(CD90), and weakly positive for c-Kit (CD117). After three-dimensional formation, the cells expressed insulin and albumin. We designated the cells as swine salivary gland-derived progenitor cells. Gene expression of insulin and albumin was significantly increased (five-fold) and that of insulin was also increased (3.8-fold) with differentiation medium with nicotinamide and/or GLP-1 treatment in spherical culture. The expressions of albumin and insulin were 1/10-fold and 1/4-fold compared to porcine hepatocytes and pancreatic endocrine cells. The differentiated SGP cells could release insulin, which were stimulated by glucose and potassium. These results indicate that swine SGP cells could differentiate into hepatocytes and beta-cells, functionally. Swine SGP cells were useful tools for therapy and analyzing endodermal regenerative models in large animals.
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PMID:Isolation of tissue progenitor cells from duct-ligated salivary glands of swine. 1757 51

The beta-selection checkpoint in alphabetaT lymphocyte development occurs at the double negative (DN) 3 (CD4(-)CD8(-)CD25(+)c-kit(-)) stage, when further differentiation requires a signal from the newly rearranged TCR beta chain. Thymocytes with mutations in key signaling molecules in the phosphatidylinositol 3-kinase-Akt pathway manifest defects in survival, proliferation, and differentiation past the beta-selection checkpoint. However, little information is available regarding the role of Akt itself in thymocyte development. In this study, we explore the role of the two Akt isoforms most highly expressed in the thymus, Akt1 and Akt2, in early T cell development. Using several complementary approaches, we find that deletion of Akt1 results in only minor defects in thymocyte development. The Akt1(-/-)Akt2(-/-) thymocytes manifest a severe developmental block at the DN3 stage and ultimately fail to repopulate the T cell compartment of an irradiated host. Further, we show that Akt1(-/-)Akt2(-/-) DN3 cells have decreased glucose uptake and die in response to TCR stimulation in vitro. Study of thymocytes from the genetically altered mice suggests that the cause of the developmental defect is due to apoptosis, partially caused by decreased cellular growth and metabolism at the DN3 stage. Our results show that Akt protects thymocytes from cell death during the beta-selection checkpoint.
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PMID:Akt1 and Akt2 are required for alphabeta thymocyte survival and differentiation. 1760 65

c-Kit tyrosine receptor kinase, a well-established stem cell marker, is expressed in a variety of tissues including the pancreas. The involvement of c-Kit in fetal rat and human endocrine pancreatic development, survival, and function has been well characterized but primarily using in vitro experimental approaches. Therefore, the aim of the current study was to examine whether deficiency of a functional c-Kit receptor would have physiological and functional implications in vivo. We characterized the c-Kit mutant mouse, c-Kit(W-v/+), to evaluate the in vivo role of c-Kit in beta-cell growth and function. Here we report that male c-Kit(W-v/+) mice, at 8 wk of age, showed high fasting blood glucose levels and impaired glucose tolerance, which was associated with low levels of insulin secretion after glucose stimulation in vivo and in isolated islets. Morphometric analysis revealed that beta-cell mass was significantly reduced (50%) in male c-Kit(W-v/+) mice when compared with controls (c-Kit(+/+)) (P < 0.05). In parallel, a reduction in pancreatic duodenal homeobox-1 and insulin gene expression in whole pancreas as well as isolated islets of c-Kit(W-v/+) male mice was noted along with a decrease in pancreatic insulin content. Furthermore, the reduction in beta-cell mass in male c-Kit(W-v/+) mice was associated with a decrease in beta-cell proliferation. Interestingly, these changes were not observed in female c-Kit(W-v/+) mice until 40 wk of age. Our results clearly demonstrate that the c-Kit receptor is involved in the regulation of glucose metabolism, likely through an important role in beta-cell development and function.
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PMID:c-Kit in early onset of diabetes: a morphological and functional analysis of pancreatic beta-cells in c-KitW-v mutant mice. 1767 21

The present study was designed to investigate the relationship between pre-mating nutrition and the relative amounts of a panel of developmentally relevant genes in ovine oocytes and granulosa cells. Cast age ewes were fed a ration providing 0.5x (0.5 M) or 1.5x (1.5 M) live weight maintenance requirements for 2 weeks before slaughter. The ewes were synchronized and superovulated with FSH and pregnant mares serum gonadotropin. At slaughter, oocytes and granulosa cells were aspirated from follicles >2 mm in diameter and the relative abundance of 8 and 17 transcripts in oocytes and granulosa cells respectively were analyzed by semi-quantitative RT-PCR. In the oocytes, no differences between groups were observed for five transcripts (GDF9, BMP15, c-kit, glucose transporter 1 (SLC2A1), and hexokinase 1), but a lower amount of glucose transporter 3 (SLC2A3), sodium/glucose cotransporter 1 (SLC5A1), and Na(+)/K(+) ATPase mRNAs was detected in the 0.5 M group. Increased expression of PTGS2, HAS2, and the leptin receptor long form was observed in granulosa cells from the 0.5 M group. No differences between groups were observed for the other transcripts (early growth response factor-1, estrogen receptor-alpha, LH and FSH receptors, gremlin 1, pentraxin 3, KIT ligand, glucose transporters 1, 3, and 8, IGF1, IGF1 receptor, leptin receptor, and tumor necrosis factor-stimulated gene 6). Expression of leptin and sodium/glucose cotransporter 1 was not detected in both groups. The present data indicate that pre-mating nutrition is associated with alteration in the mRNA content in oocytes and surrounding follicle cells in ewes, which may account for the reduced reproductive performance typical of ewes that are fed a restricted ration for a short period of time before mating.
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PMID:Effects of pre-mating nutrition on mRNA levels of developmentally relevant genes in sheep oocytes and granulosa cells. 1851 15

Persistent hyperglycemia in diabetes causes endothelial cell dysfunction. Exposure to high levels of glucose, which mimics hyperglycemia, induced expression of microRNA 221 (miR-221) but reduced expression of c-kit, the receptor for stem cell factor in human umbilical vein endothelial cells (HUVECs). In addition, high glucose treatment impaired endothelial cell migration. Incubation with the antisense miR-221 oligonucleotide AMO-221 reduced expression of miR-221 and restored c-kit protein expression in HUVECs treated with high levels of glucose. Furthermore, AMO-221 treatment abolished the inhibitory effect of high glucose exposure on HUVECs transmigration. Thus, under hyperglycemic conditions, miR-221 is induced in HUVECs, which consequently triggers inhibition of c-kit and impairment of HUVECs migration. These findings suggest that manipulation of the miR-221-c-kit pathway may offer a novel strategy for treatment of vascular dysfunction in diabetic patients.
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PMID:MicroRNA-221 regulates high glucose-induced endothelial dysfunction. 1935 99

There are only a few immunohistochemical markers that are useful for differentiating thymic carcinomas from type B3 thymomas. The purpose of this study is to examine the additional markers that would be useful for differentiating between thymic carcinoma and thymoma type B3. We performed a tissue microarray analysis of surgically resected thymic tumor specimens from 12 cases of thymic carcinoma, 7 cases of type B3 thymoma, and 68 cases of other types of thymoma. Immunostaining using 49 antibodies was scored based on staining intensity and the percentage of cells that stained positive. Seven proteins that were selected by the staining scores, namely, GLUT-1 (167 vs 4), CA-IX (110 vs 15), c-kit (162 vs 44), CD5 (33 vs 0), MUC-1 (54 vs 0), CEA (42 vs 0), and CK18 (110 vs 42), were significantly higher in the thymic carcinomas than in the type B3 thymomas. The staining sensitivity and specificity of the antibodies for thymic carcinoma were GLUT-1, sensitivity 72% and specificity 100%; CA-IX, 58 and 71%; c-kit, 72 and 85%; CD5, 33 and 100%; CK18, 58 and 71%; MUC-1, 25 and 100%; and CEA, 33 and 100%. Glucose transporter 1 (GLUT-1) is the best marker for thymic carcinoma because it had the highest sensitivity and specificity. Positive immunostaining for a combination of three markers, namely, GLUT-1, CD5, and CEA, enabled differentiation of thymic carcinoma with 91.6% sensitivity and 100% specificity. In conclusion, we identified GLUT-1 as an additional marker that will be useful for differentiating thymic carcinoma from type B3 thymoma, especially in biopsy specimens that have been crushed or are otherwise difficult to examine morphologically in thymic tumors.
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PMID:Immunohistochemical differential diagnosis between thymic carcinoma and type B3 thymoma: diagnostic utility of hypoxic marker, GLUT-1, in thymic epithelial neoplasms. 1964 82

Pluripotent mesenchymal stem-like cell lines were established from lungs of 3-4 months old aborted fetus. The cells present the high ex vivo expansion potential of MSC, a typical fibroblast-like morphology and proliferate up to 15 passages without displaying clear changes in morphology. Immunological localization and flow cytometry analyses showed that these cells are positive for OCT4, c-Kit, CD11, CD29, CD44, telomerase, CD106, CD105, CD166, and SSEA1, weakly expression or negative for SSEA1, SSEA3, SSEA4, CD34, CD105 and CD106. These cells can give rise to the adipogenic as evidenced by accumulation of lipid-rich vacuoles within cells identified by Oil-red O when they were induced with 0.5 mM isobutylmethylxanthine, 200 microM indomethacin, 10(-6)M dexamethasone, and 10 microg/ml of insulin in high-glucose DMEM. Osteogenic lineage cells were generated in 0.1 microM dexamethasone, 50 microg/ml ascorbic acid, 10 mM beta-glycerophosphate, which are shaped as the osteoblastic morphology, expression of alkaline phosphatase (AP), and the formation of a mineralized extracellular matrix identified by Alizarin Red staining. Neural cells are observed when the cultures were induced with 2-mercapometal, which are positive for nestin, NF-100, MBP and GFAP. Additionally, embryoid bodies (EBs) and sperm like cells are obtained in vitro differentiation of these lung MSCs induced with 10(-5)M retinoic acid (RA). These results demonstrated that these MSCs are pluripotent and may provide an in vitro model to study germ-cell formation and also as a potential source of sperms for male infertility.
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PMID:Characterization of mesenchymal stem cells (MSCs) from human fetal lung: potential differentiation of germ cells. 1965 22

There is a high prevalence of hypertension and hypertension-related vascular disease in humans. Studies show that the expression of stem cell factor (SCF)/c-kit signalling proteins is relatively high during blood vessel repair. The aim of this study was to investigate the relationship between blood pressure (BP) and the expression of SCF/c-kit in peripheral blood. We carried out a cross-sectional analysis of 141 subjects in the health examination centre of our hospital. Information including waist circumference, BP, plasma glucose and serum lipids for each subject was collected. Endothelin-1 (ET-1) and tumour necrosis factor-alpha (TNF-alpha) levels in peripheral blood were determined by radio-immunity assay. Expression levels of SCF and its receptor, c-kit, in peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA). We found a positive correlation between plasma SCF/c-kit levels and BP in these patients (SCF: hypertension 907.1+/-52.3 vs pre-hypertension 834.6+/-47.6 vs normal control 768.8+/-44.1 ng l(-1); c-kit: hypertension 13.2+/-1.6 vs pre-hypertension 11.1+/-2.1 vs normal control 9.6+/-1.5 mg l(-1), P<0.01). SCF/c-kit levels were also positively correlated with ET-1 and TNF-alpha levels (ET-1: hypertension 155.5+/-12.1 vs pre-hypertension 142.0+/-11.2 vs normal control 117.9+/-10.3 ng l(-1); TNF-alpha: hypertension 14.7+/-3.9 vs pre-hypertension 11.6+/-4.2 vs normal control 8.1+/-2.8 ng l(-1), P<0.01). Multiple linear regression analyses showed that SCF, c-kit and ET-1 are independent predictors for systolic blood pressure, and that SCF, c-kit, ET-1 and TNF-alpha are independent predictors for diastolic blood pressure. SCF/c-kit levels increase with BP levels are positively correlated with ET-1 and TNF-alpha levels.
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PMID:Relationship between stem cell factor/c-kit expression in peripheral blood and blood pressure. 1967 87

The mechanism involved in the prosurvival effect of interleukin-3 on the human acute myeloid leukaemia cell line M07e is investigated. A decrease in intracellular reactive oxygen species (ROS) content, glucose transport activity and cell survival was observed in the presence of inhibitors of plasma membrane ROS sources, such as diphenylene iodonium and apocynin, and by small interference RNA for Nox2. Moreover, IL-3 incubation stimulated the synthesis of Nox2 cytosolic sub-unit p47phox and glucose transporter Glut1. Thus, the inhibition of ROS generation by Nox inhibitors stimulated apoptosis showing that ROS production, induced by IL-3 via Nox2, protects leukaemic cells from cell death. Also incubation with receptor tyrosine kinase inhibitors, such as anti-leukaemic drugs blocking the stem cell factor receptor (c-kit), showed similar effects, hinting that IL-3 transmodulates c-kit phosphorylation. These mechanisms may play an important role in acute myeloid leukaemia treatment, representing a novel therapeutic target.
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PMID:NAD(P)H oxidase isoform Nox2 plays a prosurvival role in human leukaemia cells. 1970 18


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