Prostaglandins and calprotectin are genetically and functionally linked to the Inflammatory Bowel Diseases.

Background: Genome wide association studies (GWAS) have identified and validated more than 200 genomic loci associated with the inflammatory bowel disease (IBD), although for most the causal gene remains unknown. Given the importance of myeloid cells in IBD pathogenesis, the current study aimed to uncover the role of genes within IBD genetic loci that are endogenously expressed in this cell lineage.

Methods: The open reading frames (ORF) of 42 genes from IBD-associated loci were expressed via lentiviral transfer in the THP-1 model of human monocytes and the impact of each of these on the cell's transcriptome was analyzed using a RNA sequencing-based approach.

Functional screen of inflammatory bowel disease genes reveals key epithelial functions.

Background: Genetic studies have been tremendously successful in identifying genomic regions associated with a wide variety of phenotypes, although the success of these studies in identifying causal genes, their variants, and their functional impacts has been more limited.

Methods: We identified 145 genes from IBD-associated genomic loci having endogenous expression within the intestinal epithelial cell compartment. We evaluated the impact of lentiviral transfer of the open reading frame (ORF) of these IBD genes into the HT-29 intestinal epithelial cell line via transcriptomic analyses.

Cardiac resident nestin(+) cells participate in reparative vascularisation.

The rodent heart contains a population of nestin((+)) cells derived from the embryonic neural crest and migrate to the scar after myocardial infarction (MI). The present study tested the hypothesis that intron 2 of the nestin gene drives expression and a subpopulation of nestin((+)) cells participate in reparative vascularisation. The directed expression of the green fluorescent protein (GFP) by the second intron of the nestin gene identified GFP/nestin((+)) cells intercalated among ventricular myocytes in the heart of normal transgenic mice.

The plating of rat scar myofibroblasts on matrigel unmasks a novel phenotype; the self assembly of lumen-like structures.

During tissue healing, the primary role of myofibroblasts involves the synthesis and deposition of collagen. However, it has also been reported that selective populations of myofibroblasts can acquire the phenotype and/or differentiate to other cells types. The present study tested the hypothesis that myofibroblasts isolated from the scar of the ischemically damaged rat heart can recapitulate an endothelial cell-like response when plated in a permissive in vitro environment.

Nestin expression is lost in ventricular fibroblasts during postnatal development of the rat heart and re-expressed in scar myofibroblasts.

Studies have reported that the intermediate filament protein nestin was expressed in various non-stem/progenitor cells during development, downregulated during postnatal growth and re-expressed following injury. The present study tested the hypothesis that an analogous paradigm was prevalent for ventricular fibroblasts. In the neonatal rat heart, nestin protein levels were significantly higher than the adult heart and the isolation of cardiac cells revealed a selective expression in ventricular fibroblasts.