璧勮涓績 > 浜у搧鏂囩尞闆?> Development (31)

  鉁旀湰綃囪鏂囦嬌鐢ㄥ崕鑱斾駭鍝侊細Human OneArray  
 European Journal Of Cell Biology. 2010, 89(7):537-46. doi: 10.1016/j.ejcb.2010.01.005.
 Expression of the homeobox gene, HOPX, is modulated by cell differentiation in human keratinocytes and is involved in the expression of differentiation markers. 
 Jun-mo Yang, Seon Mi Sim, Hyo-yeon Kim, Geon Tae Park.
  Abstract
Homeodomain only protein X (HOPX), an unusual homeodomain protein, was originally identified as a key regulator of cardiac development. We first demonstrated that the expression of HOPX was dependent on the differentiation of human keratinocytes and has an effect on the expression of differentiation markers. HOPX was suppressed in proliferating human keratinocytes and was gradually induced by calcium-triggered differentiation of human keratinocytes. In the epidermis, HOPX is highly expressed in the terminally differentiated suprabasal layers. Among the transcript variants of HOPX, the variant 3 driven by promoter A was the main transcript and it was regulated by cell differentiation in human keratinocytes. The expression of HOPX was induced through the phorbol-12-myristate-13-acetate (PMA)-dependent protein kinase C (PKC) signaling pathway, and not by the demethylating agent, 5-aza-dC (5-aza-2'-deoxycitidine) suggesting the suppression of HOPX is not associated with DNA methylation in human keratinocytes. The RNA interference (RNAi) silencing experiment showed that the knockdown of HOPX expression resulted in the increase of such differentiation markers as involucrin and loricrin. Exogenous expression of HOPX down-regulated the expression of differentiation marker genes in immortalized human keratinocytes (HaCaT). Collectively, HOPX is modulated by cell differentiation in human keratinocytes and this might contribute to homeostasis of keratinocytes by controlling differentiation-dependent genes.
   

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  鉁旀湰綃囪鏂囦嬌鐢ㄥ崕鑱斾駭鍝侊細Mouse&Rat miRNA OneArray  
 Cellular And Molecular Biology Letters. DOI: 10.1515/cmble-2015-0034.
 Mechanical Strain Affects Some Microrna Profiles in Pre-Oeteoblasts
 
 
 
  Abstract
MicroRNAs (miRNAs) are important regulators of cell proliferation, differentiation and function. Mechanical strain is an essential factor for osteoblast proliferation and differentiation. A previous study revealed that a physiological mechanical tensile strain of 2500 microstrain (渭蔚) at 0.5 Hz applied once a day for 1 h over 3 consecutive days promoted osteoblast differentiation. However, the mechanoresponsive miRNAs of these osteoblasts were not identified. In this study, we applied the same mechanical tensile strain to in vitro cultivated mouse MC3T3-E1 pre-osteoblasts and identified the mechanoresponsive miRNAs. Using miRNA microarray and qRT-PCR assays, the expression patterns of miRNAs were evaluated and 5 of them were found to be significantly different between the mechanical loading group and the control group: miR-3077-5p, 3090-5p and 3103-5p were significantly upregulated and miR-466i-3p and 466h-3p were downregulated. Bioinformatics analysis revealed possible target genes for these differentially expressed miRNAs. Some target genes correlated with osteoblast differentiation. These findings indicated that the mechanical strain changed the expression levels of these miRNAs. This might be a potential regulator of osteoblast differentiation and responses to mechanical strain.
   

  鉁旀湰綃囪鏂囦嬌鐢ㄥ崕鑱斾駭鍝侊細Mouse OneArray  
 Science Signaling. 2015, 8(375):ra41. doi: 10.1126/scisignal.2005781.
 Actin cytoskeletal remodeling with protrusion formation is essential for heart regeneration in Hippo-deficient mice
 
 
 Yuka Morikawa, Min Zhang, Todd Heallen, John Leach, Ge Tao, Yang Xiao, Yan Bai, Wei Li, James T. Willerson, James F. Martin
  Abstract
The mammalian heart regenerates poorly, and damage commonly leads to heart failure. Hippo signaling is an evolutionarily conserved kinase cascade that regulates organ size during development and prevents adult mammalian cardiomyocyte regeneration by inhibiting the transcriptional coactivator Yap, which also responds to mechanical signaling in cultured cells to promote cell proliferation. To identify Yap target genes that are activated during cardiomyocyte renewal and regeneration, we performed Yap chromatin immunoprecipitation sequencing (ChIP-Seq) and mRNA expression profiling in Hippo signaling鈥揹eficient mouse hearts. We found that Yap directly regulated genes encoding cell cycle progression proteins, as well as genes encoding proteins that promote F-actin polymerization and that link the actin cytoskeleton to the extracellular matrix. Included in the latter group were components of the dystrophin glycoprotein complex, a large molecular complex that, when defective, results in muscular dystrophy in humans. Cardiomyocytes near the scar tissue of injured Hippo signaling鈥揹eficient mouse hearts showed cellular protrusions suggestive of cytoskeletal remodeling. The hearts of mdx mutant mice, which lack functional dystrophin and are a model for muscular dystrophy, showed impaired regeneration and cytoskeleton remodeling, but normal cardiomyocyte proliferation, after injury. Our data showed that, in addition to genes encoding cell cycle progression proteins, Yap regulated genes that enhance cytoskeletal remodeling. Thus, blocking the Hippo pathway input to Yap may tip the balance so that Yap responds to mechanical changes associated with heart injury to promote repair.
   

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  鉁旀湰綃囪鏂囦嬌鐢ㄥ崕鑱斾駭鍝侊細Human OneArray  
 Bmc Cancer. DOI 10.1186/s12885-015-1671-5.
 Upregulation of MicroRNA-19b predicts good prognosis in patients with hepatocellular carcinoma presenting with vascular invasion or multifocal disease
 
 
 
  Abstract
Background After surgical resection of hepatocellular carcinoma (HCC), recurrence is common, especially in patients presenting with vascular invasion or multifocal disease after curative surgery. Consequently, we examined the expression pattern and prognostic value of miR-19b in samples from these patients. Methods We performed a miRNA microarray to detect differential expression of microRNAs (miRNAs) in 5 paired samples of HCC and non-tumoral adjacent liver tissue and a quantitative real-time polymerase chain reaction (PCR) analysis to validate the results in 81 paired samples of HCC and adjacent non-tumoral liver tissues. We examined the associations of miR-19b expression with clinicopathological parameters and survival. MiR-19b was knocked down in Hep3B and an mRNA microarray was performed to detect the affected genes. Results In both the miRNA microarray and real-time PCR, miR-19b was significantly overexpressed in the HCC tumor compared with adjacent non-tumor liver tissues (P < 0.001). The expression of miR-19b was significantly higher in patients who were disease-free 2 years after surgery (P < 0.001). High miR-19b expression levels were associated with higher 偽-fetoprotein levels (P = 0.017). In the log-rank test, high miR-19b was associated with better disease-free survival (median survival 37.107 vs. 11.357; P = 0.022). In Cox multivariate analysis, high miR-19b predicted better disease-free survival and overall survival (hazards ratio [HR] = 0.453, 95 % confidence interval [CI] = 0.245鈥?.845, P = 0.013; HR = 0.318, CI = 0.120鈥?.846, P = 0.022, respectively). N-myc downstream regulated 1 (NDRG1) was downregulated, while epithelial cell adhesion molecule (EPCAM), hypoxia-inducible factor 1-alpha (HIF1A), high-mobility group protein B2 (HMGB2), and mitogen activated protein kinase 14 (MAPK14) were upregulated when miR-19b was knocked down in Hep3B. Conclusions The overexpression of miR-19b was significantly correlated with better disease-free and overall survival in patients with HCC presenting with vascular invasion or multifocal disease after curative surgery. MiR-19b may influence the expression of NDRG1, EPCAM, HMGB2, HIF1A, and MAPK14.
   

  鉁旀湰綃囪鏂囦嬌鐢ㄥ崕鑱斾駭鍝侊細Human OneArray  
 Amino Acids. doi: 10.1007/s00726-015-1956-7. Epub 2015 Mar 24..
 Homocysteine thiolactone and N-homocysteinylated protein induce pro-atherogenic changes in gene expression in human vascular endothelial cells
 
 
 
  Abstract
Genetic or nutritional deficiencies in homocysteine (Hcy) metabolism lead to hyperhomocysteinemia (HHcy) and cause endothelial dysfunction, a hallmark of atherosclerosis. In addition to Hcy, related metabolites accumulate in HHcy but their role in endothelial dysfunction is unknown. Here, we examine how Hcy-thiolactone, N-Hcy-protein, and Hcy affect gene expression and molecular pathways in human umbilical vein endothelial cells. We used microarray technology, real-time quantitative polymerase chain reaction, and bioinformatic analysis with PANTHER, DAVID, and Ingenuity Pathway Analysis (IPA) resources. We identified 47, 113, and 30 mRNAs regulated by N-Hcy-protein, Hcy-thiolactone, and Hcy, respectively, and found that each metabolite induced a unique pattern of gene expression. Top molecular pathways affected by Hcy-thiolactone were chromatin organization, one-carbon metabolism, and lipid-related processes [−log(P value) = 20鈥?1]. Top pathways affected by N-Hcy-protein and Hcy were blood coagulation, sulfur amino acid metabolism, and lipid metabolism [−log(P value)] = 4鈥?1; also affected by Hcy-thiolactone, [−log(P value) = 8鈥?4]. Top disease related to Hcy-thiolactone, N-Hcy-protein, and Hcy was 鈥榓therosclerosis, coronary heart disease鈥?[−log(P value) = 9鈥?6]. Top-scored biological networks affected by Hcy-thiolactone (score = 34鈥?0) were cardiovascular disease and function; those affected by N-Hcy-protein (score = 24鈥?5) were 鈥榮mall molecule biochemistry, neurological disease,鈥?and 鈥榗ardiovascular system development and function鈥? and those affected by Hcy (score = 25鈥?7) were 鈥榓mino acid metabolism, lipid metabolism,鈥?鈥榗ellular movement, and cardiovascular and nervous system development and function.鈥?These results indicate that each Hcy metabolite uniquely modulates gene expression in pathways important for vascular homeostasis and identify new genes and pathways that are linked to HHcy-induced endothelial dysfunction and vascular disease.
   

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