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.
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:1:1000-1:5000, IHC:1:25-1:100
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: aFGF and bFGF display 55% homology which is limited, however, to a few functional domains. The structure of aFGF, revealed by X-ray crystallography, shows a similar folding structure as IL1. Because aFGF binds to the same receptor as bFGF, aFGF displays more or less the same spectrum of activities. It is, however, generally less active than bFGF in similar assays. FGF receptors are encoded by a gene family consisting of at least four receptor tyrosine kinases that transduce signals important in a variety of developmental and physiological processes related to cell growth and differentiation. Recombinant Human FGF1 is a single polypeptide of 16 kDa.
Description: aFGF and bFGF display 55% homology which is limited, however, to a few functional domains. The structure of aFGF, revealed by X-ray crystallography, shows a similar folding structure as IL1. Because aFGF binds to the same receptor as bFGF, aFGF displays more or less the same spectrum of activities. It is, however, generally less active than bFGF in similar assays. FGF receptors are encoded by a gene family consisting of at least four receptor tyrosine kinases that transduce signals important in a variety of developmental and physiological processes related to cell growth and differentiation. Recombinant Human FGF1 is a single polypeptide of 16 kDa.
Description: aFGF and bFGF display 55% homology which is limited, however, to a few functional domains. The structure of aFGF, revealed by X-ray crystallography, shows a similar folding structure as IL-1. Because aFGF binds to the same receptor as bFGF, aFGF displays more or less the same spectrum of activities. It is, however, generally less active than bFGF in similar assays. FGF receptors are encoded by a gene family consisting of at least four receptor tyrosine kinases that transduce signals important in a variety of developmental and physiological processes related to cell growth and differentiation.
Description: aFGF and bFGF display 55 % homology which is limited, however, to a few functional domains. The structure of aFGF, revealed by X-ray crystallography, shows a similar folding structure as IL-1. Because aFGF binds to the same receptor as bFGF, aFGF displays more or less the same spectrum of activities. It is, however, generally less active than bFGF in similar assays. FGF receptors are encoded by a gene family consisting of at least four receptor tyrosine kinases that transduce signals important in a variety of developmental and physiological processes related to cell growth and differentiation.
Description: aFGF and bFGF display 55 % homology which is limited, however, to a few functional domains. The structure of aFGF, revealed by X-ray crystallography, shows a similar folding structure as IL-1. Because aFGF binds to the same receptor as bFGF, aFGF displays more or less the same spectrum of activities. It is, however, generally less active than bFGF in similar assays. FGF receptors are encoded by a gene family consisting of at least four receptor tyrosine kinases that transduce signals important in a variety of developmental and physiological processes related to cell growth and differentiation.
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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.
Felicia
