Project description:A/J mice are genetically predisposed to spontaneous and/or chemically-induced lung tumors while C57BL/6J (B6) mice are resistant. This genetic disparity provides a unique scenario to identify molecular mechanisms associated with the lung response to welding fume at the transcriptome level. Overall design: Four mice per group were exposed four times by pharyngeal aspiration to 5mg/kg mild steel (MS) fume, stainless steel (SS) fume, or saline vehicle and were necropsied 28 days and 16 weeks after the last exposure. Whole lung microarray using Illumina Mouse Ref-8 version 1.1 expression beadchips was done.
Project description:Endothelial cell (EC)-enriched protein coding genes, such as endothelial nitric oxide synthase (eNOS), define quintessential EC-specific physiologic functions. It is not clear whether long noncoding RNAs (lncRNAs) also define cardiovascular cell-type specific phenotypes, especially in the vascular endothelium. Here, we report the existence of a set of EC-enriched lncRNAs and define a role for STEEL (spliced transcript – endothelial enriched lncRNA) in angiogenic potential, macrovascular/microvascular identity and shear stress responsiveness. STEEL is expressed from the terminus of the HOXD locus and is transcribed antisense to HOXD transcription factors. STEEL RNA increases the number and integrity of de novo perfused microvessels in an in vivo model and augments angiogenesis in vitro. The STEEL RNA is polyadenylated, nuclear-enriched and has microvascular predominance. Functionally, STEEL regulates a number of genes in diverse endothelial cells. Of interest, STEEL upregulates both eNOS and the transcription factor Kruppel-like factor 2 (KLF2), and is subject to feedback inhibition by both eNOS and shear-augmented KLF2. Mechanistically, STEEL upregulation of eNOS and KLF2 is transcriptionally mediated, in part, via interaction of chromatin-associated STEEL with the poly-ADP ribosylase, PARP1. For instance, STEEL recruits PARP1 to the KLF2 promoter. This work identifies a role for EC-enriched lncRNAs in the phenotypic adaptation of ECs to both body position and hemodynamic forces, and establishes a newer role for lncRNAs in the transcriptional regulation of EC identity.
2018-02-28 | PXD008581 | Pride
Project description:Corrosion and biofouling in brackish seawater environment: comparison between stainless steel grades
Project description:To determine the role of STEEL in endothelial cell (EC) gene regulation, gene expression analysis was conducted on control and STEEL siRNA-treated human dermal microvascular endothelial cells (HMVECs) and human umbilical vein endothelial cells (HUVECs). A total of 225 protein-coding genes were downregulated and 80 were upregulated when both EC types were grouped for analysis. In HMVEC alone, 544 protein-coding genes were downregulated and 218 were upregulated. In HUVEC alone, 177 protein-coding genes were downregulated and 125 were upregulated. Prominently, STEEL siRNA depletion results in the downregulation of two notable protein-coding genes, eNOS and KLF2, which are modulated in ECs subjected to continuous laminar shear stress. Overall design: HUVECs and HMVECs were treated with control siRNA or STEEL siRNA for 48 hours. Subsequently, these samples were subjected to gene expression analysis using a custom agilent microarray that recognizes 30215 protein-coding transcripts and 33045 lncRNAs.
Project description:Transcriptional profiles of Salmonella Typhimurium str. ST4/74 air-dried onto stainless steel for 4 h was compared to an early stationary phase (ESP) culture control. Cells that had been air-dried for 4 h were then subsequently rehydrated with water for a 30 min period, after which the transcriptional profile was compared to an ESP control. Carried out using 2 biological replicates for each sample; hybridised in a two-channel hybridization against Salmonella genomic DNA as the comparator/reference.