Background: Intermediate filament proteins that construct the nuclear lamina protein lamin cell including A / C is encoded by the gene LMNA, and is involved in fundamental processes such as nuclear structure, gene expression and signal transduction. LMNA mutations predominantly affect the mesoderm-derived cell lineages in diseases collectively referred to as laminopathies which include dilated cardiomyopathy with conduction defects, various forms of muscular dystrophy and premature aging syndromes as Hutchinson-Gilford Progeria Syndrome. At present, our understanding of the molecular mechanisms that regulate tissue-specific manifestations of laminopathies still limited.
Methods: To gain more insight into the molecular mechanisms of a novel splice-site mutations in LMNA (c.357-2A> G) in a family affected by heart disease, we do deep RNA sequencing and analysis for the nine lines derived fibroblast samples three patients with cardiomyopathy, three unaffected family members, and three unrelated individuals not affected. We validated our findings by the study of quantitative PCR and protein.
Results: We identified eight genes were significantly differentially expressed between fibroblasts mutant and non-mutant, which included downregulated factor insulin growth factor binding protein 5 (IGFBP5) in patient samples. ERK pathway analysis indicates involvement / MAPK signaling pathways consistent with previous studies. We found no significant differences in gene expression of lamin A / C and B-type lamins between groups. In the mutant fibroblasts, RNA-seq confirmed that only LMNA predominantly expressed wild-type allele, and Western blot showed normal levels of the protein lamin A / C
Conclusion: IGFBP5 can contribute in maintaining homeostasis pathway signaling, which may cause the molecular and structural abnormalities is important in the network are not affected as fibroblasts. the mechanism of compensation of other nuclear membrane protein was not found. Our results also showed that only one copy of the wild allele kind enough to normal levels of the protein lamin A / C to maintain physiological functions in the cell type affected. This indicates that the affected cell types such as heart tissue may be more sensitive to haploinsufficiency of lamin A / C. These results provide insight into the molecular mechanisms of diseases with a possible explanation for tissue specificity LMNA related dilated cardiomyopathy.
Gene expression profiling of fibroblasts in a family with LMNA-related cardiomyopathy reveals molecular pathways implicated in disease pathogenesis
A novel multi-targeted tyrosine kinase inhibitor in combination with irinotecan anlotinib have in-vitro anti-tumor activity against lung cancer, small cell lung human
Anlotinib is a multi-targeted tyrosine kinase inhibitor developed independently in China. biological effects remain unclear in small cell lung cancer (SCLC). The current study aimed to evaluate the effects of anlotinib in combination with irinotecan in H446 and H2227 SCLC cell lines and provide new treatment strategies for SCLC. the growth of cells of the two cell lines was inhibited by anlotinib, irinotecan and the combination with a dose-dependent manner.
Human Fibroblast Growth Factor 1, Acidic (FGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Bovine Fibroblast Growth Factor 1, Acidic (FGF1) in samples from serum, plasma or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Bovine Fibroblast Growth Factor 1, Acidic (FGF1) in samples from serum, plasma or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Chicken Fibroblast Growth Factor 1, Acidic (FGF1) in samples from serum, plasma or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Chicken Fibroblast Growth Factor 1, Acidic (FGF1) in samples from serum, plasma or other biological fluids.
Human Fibroblast Growth Factor 1, Acidic (FGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Human Fibroblast Growth Factor 1, Acidic (FGF1) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Human Fibroblast Growth Factor 1, Acidic (FGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Human Fibroblast Growth Factor 1, Acidic (FGF1) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Mouse Fibroblast Growth Factor 1, Acidic (FGF1) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Mouse Fibroblast Growth Factor 1, Acidic (FGF1) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Porcine Fibroblast Growth Factor 1, Acidic (FGF1) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Porcine Fibroblast Growth Factor 1, Acidic (FGF1) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Rat Fibroblast Growth Factor 1, Acidic (FGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Rat Fibroblast Growth Factor 1, Acidic (FGF1) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Rat Fibroblast Growth Factor 1, Acidic (FGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Rat Fibroblast Growth Factor 1, Acidic (FGF1) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A polyclonal antibody against FGF1. Recognizes FGF1 from Human, Mouse, Rat. This antibody is Unconjugated. Tested in the following application: IHC, ELISA;IHC:1/100-1/300.ELISA:1/10000
Description: A polyclonal antibody against FGF1. Recognizes FGF1 from Human, Mouse. This antibody is Unconjugated. Tested in the following application: ELISA, WB, IHC, IF; Recommended dilution: WB:1:200-1:1000, IHC:1:20-1:500, IF:1:50-1:200
Description: A polyclonal antibody against FGF1. Recognizes FGF1 from Human. This antibody is Unconjugated. Tested in the following application: ELISA, IHC, IF; Recommended dilution: IHC:1:20-1:500, IF:1:50-1:200
Description: A polyclonal antibody against FGF1. Recognizes FGF1 from Human, Mouse, Rat. This antibody is Unconjugated. Tested in the following application: ELISA, IHC
Description: A polyclonal antibody against Fgf1. Recognizes Fgf1 from Human, Mouse. This antibody is Unconjugated. Tested in the following application: ELISA, WB, IHC; Recommended dilution: WB:1:500-1:2000, IHC:1:20-1:200
Description: A polyclonal antibody against FGF1. Recognizes FGF1 from Human, Mouse, Rat. This antibody is Unconjugated. Tested in the following application: ELISA, IHC;ELISA:1:2000-1:10000, IHC:1:50-1:200
Description: A polyclonal antibody against FGF1. Recognizes FGF1 from Human, Mouse, Rat. This antibody is Unconjugated. Tested in the following application: ELISA, IHC;ELISA:1:1000-1:5000, IHC:1:25-1:100
Description: The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This protein functions as a modifier of endothelial cell migration and proliferation, as well as an angiogenic factor. It acts as a mitogen for a variety of mesoderm- and neuroectoderm-derived cells in vitro, thus is thought to be involved in organogenesis. Multiple alternatively spliced variants encoding different isoforms have been described.
Description: The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This protein functions as a modifier of endothelial cell migration and proliferation, as well as an angiogenic factor. It acts as a mitogen for a variety of mesoderm- and neuroectoderm-derived cells in vitro, thus is thought to be involved in organogenesis. Multiple alternatively spliced variants encoding different isoforms have been described.
Description: FGF acidic is a 17 kDa nonglycosylated member of the FGF family of mitogenic peptides. FGF acidic, which is produced by multiple cell types, stimulates the proliferation of all cells of mesodermal origin and many cells of neuroectodermal, ectodermal, and endodermal origin. It plays a number of roles in development, regeneration, and angiogenesis. FGF-acidic is a non-glycosylated heparin binding growth factor that is expressed in the brain, kidney, retina, smooth muscle cells, bone matrix, osteoblasts, astrocytes and endothelial cells. FGF-acidic has the ability to signal through all the FGF receptors.
Description: FGF acidic, also known as ECGF, FGF-1and HBGF-1, is a non-glycosylated heparin binding growth factor that is expressed in the brain, kidney, retina, smooth muscle cells, bone matrix, osteoblasts, astrocytes and endothelial cells. It is a mitogenic peptide that is produced by multiple cell types and stimulates the proliferation of cells of mesodermal, ectodermal, and endodermal origin. Its association with heparan sulfate is a prerequisite for activation of FGF receptors. Internalized FGF acidic migrates to the nucleus where it is phosphorylated by nuclear PKC delta, exported to the cytosol, dephosphorylated, and degraded. Intracellular FGF acidic inhibits p53 activity and proapoptotic signaling.
Description: FGF acidic, also known as ECGF, FGF-1and HBGF-1, is a non-glycosylated heparin binding growth factor that is expressed in the brain, kidney, retina, smooth muscle cells, bone matrix, osteoblasts, astrocytes and endothelial cells. It is a mitogenic peptide that is produced by multiple cell types and stimulates the proliferation of cells of mesodermal, ectodermal, and endodermal origin. Its association with heparan sulfate is a prerequisite for activation of FGF receptors. Internalized FGF acidic migrates to the nucleus where it is phosphorylated by nuclear PKC delta, exported to the cytosol, dephosphorylated, and degraded. Intracellular FGF acidic inhibits p53 activity and proapoptotic signaling.
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After 72 hours of incubation, the degree of inhibition was greater in the combination group than all the single drug groups. Similar results were found when apoptosis was assessed after 12 h, but not after 6 hours of treatment. Compared with a single drug, drug combination suppressed the migration and invasion ability in two cell lines; However, there is no difference between anlotinib individual or irinotecan. Colony formation rates clearly lowered in the combination group.
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