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)

Ischemic heart disease is a leading cause of death, with few options to retain ventricular function following myocardial infarction. Hematopoietic-derived progenitor cells contribute to angiogenesis and tissue repair following ischemia reperfusion injury. Motivated by the role of bone marrow extracellular matrix (BM-ECM) in supporting the proliferation and regulation of these cell populations, we investigated BM-ECM injection in myocardial repair. In BM-ECM isolated from porcine sternum, we identified several factors important for myocardial healing, including vascular endothelial growth factor, basic fibroblast growth factor-2, and platelet-derived growth factor-BB. We further determined that BM-ECM serves as an adhesive substrate for endothelial cell proliferation. Bone marrow ECM was injected in a rat model of myocardial infarction, with and without a methylcellulose carrier gel. After one day, reduced infarct area was noted in rats receiving BM-ECM injection. After seven days we observed improved fractional shortening, decreased apoptosis, and significantly lower macrophage counts in the infarct border. Improvements in fractional shortening, sustained through 21 days, as well as decreased fibrotic area, enhanced angiogenesis, and greater c-kit-positive cell presence were associated with BM-ECM injection. Notably, the concentrations of BM-ECM growth factors were 10(3)-10(8) fold lower than typically required to achieve a beneficial effect, as reported in pre-clinical studies that have administered single growth factors alone.
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PMID:Effect of bone marrow-derived extracellular matrix on cardiac function after ischemic injury. 2281 98

Cutaneous mast cell tumours are one of the most common canine cancers. Approximately 25% of the tumours metastasise. Activating c-kit mutations are present in about 20% of tumours, but metastases occur in the absence of mutations. Tumour metastasis is associated with significantly diminished survival in spite of adjuvant chemotherapy. Available prognostic tests do not reliably predict whether a tumour will metastasise. In this study we compared the global expression profiles of 20 primary cutaneous mast cell tumours that metastasised with those of 20 primary tumours that did not metastasise. The objective was to identify genes associated with mast cell tumour metastatic progression that may represent targets for therapeutic intervention and biomarkers for prediction of tumour metastasis. Canine Gene 1.1 ST Arrays were employed for genome-wide expression analysis of formalin-fixed, paraffin-embedded biopsies of mast cell tumours borne by dogs that either died due to confirmed mast cell tumour metastasis, or were still alive more than 1000 days post-surgery. Decreased gene expression in the metastasising tumours appears to be associated with a loss of cell polarity, reduced cell-cell and cell-ECM adhesion, and increased cell deformability and motility. Dysregulated gene expression may also promote extracellular matrix and base membrane degradation, suppression of cell cycle arrest and apoptosis, and angiogenesis. Down-regulation of gene expression in the metastasising tumours may be achieved at least in part by small nucleolar RNA-derived RNA and microRNA-effected gene silencing. Employing cross-validation, a linear discriminant analysis-based classifier featuring 19 genes that displayed two-fold differences in expression between metastasising and non-metastasising tumours was estimated to classify metastasising and non-metastasising tumours with accuracies of 90-100% and 70-100%, respectively. The differential expression of 9 of the discriminator genes was confirmed by quantitative reverse transcription-PCR.
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PMID:Identification of molecular genetic contributants to canine cutaneous mast cell tumour metastasis by global gene expression analysis. 3056 30

Historically, the field of tissue engineering has been adept at modulating the chemical and physical microenvironment. This approach has yielded significant progress, but it is imperative to further integrate our understanding of other fundamental cell signaling paradigms into tissue engineering methods. Bioelectric signaling has been demonstrated to be a vital part of tissue development, regeneration, and function across organ systems and the extracellular matrix is known to alter the bioelectric properties of cells. Thus, there is a need to bolster our understanding of how matrix and bioelectric signals interact to drive cell phenotype. We examine how cardiac progenitor cell differentiation is altered by simultaneous changes in both resting membrane potential and extracellular matrix composition. Pediatric c-kit+ cardiac progenitor cells were differentiated on fetal or adult cardiac extracellular matrix while being treated with drugs that alter resting membrane potential. Smooth muscle gene expression was increased with depolarization and decreased with hyperpolarization while endothelial and cardiac expression were unchanged. Early smooth muscle protein expression is modified by matrix developmental age, with fetal ECM appearing to amplify the effects of resting membrane potential. Thus, combining matrix composition and bioelectric signaling represents a potential alternative for guiding cell behavior in tissue engineering and regenerative medicine.
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PMID:The effects of membrane potential and extracellular matrix composition on vascular differentiation of cardiac progenitor cells. 3282 93