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Non-Esterified Fatty Acids of Primary Sclerosing Cholangitis (part II)

ABSTRACT: To qualitatively and quantitatively analyze enterohepatically-circulated molecules using targeted free fatty acid concentrations of peripheral blood collected from primary sclerosing cholangitis (PSC) patients compared to normal and diseased controls. There are three groups of patients. (1) Normal donor controls (ND), (2) Patients with Primary Sclerosing Cholangitis (PSC), and (3) Disease Controls (DC) which are patients with liver disease other than PSC.

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Blood

SUBMITTER: Steven O'Hara

PROVIDER: ST000996 | MetabolomicsWorkbench | Wed Jul 05 00:00:00 BST 2017

REPOSITORIES: MetabolomicsWorkbench

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Project description:Dupuytren's contracture (DC) is the most common inherited connective tissue disease of humans and is hypothesized to be associated with aberrant wound healing of the palmar fascia. Fibroblasts and myofibroblasts are believed to play an important role in the genesis of DC and the fibroproliferation and contraction that are hallmarks of this disease. This study compares the gene expression profiles of fibroblasts isolated from DC patients and controls in an attempt to identify key genes whose regulation might be significantly altered in fibroblasts found within the palmar fascia of Dupuytren's patients. Total RNA isolated from diseased palmar fascia (DC) and normal palmar fascia (obtained during carpal tunnel release; 6 samples per group) was subjected to quantitative analyses using two different microarray platforms (GE Code Link™ and Illumina™) to identify and validate differentially expressed genes. The data obtained was analyzed using The Significance Analysis of Microarrays (SAM) software through which we identified 69 and 40 differentially regulated gene transcripts using the CodeLink™ and Illumina™ platforms, respectively. The CodeLink™ platform identified 18 upregulated and 51 downregulated genes. Using the Illumina™ platform, 40 genes were identified as downregulated, eleven of which were identified by both platforms. Quantitative RT-PCR confirmed the downregulation of three high-interest candidate genes which are all components of the extracellular matrix: proteoglycan 4 (PRG4), fibulin-1 (FBLN-1) transcript variant D, and type XV collagen alpha 1 chain. Overall, our study has identified a variety of candidate genes that may be involved in the pathophysiology of Dupuytren's contracture and may ultimately serve as attractive molecular targets for alternative therapies. Dupuytren's contracture and may ultimately serve as attractive molecular targets for alternative therapies. 6 Samples from carpal-tunnel derived fibroblasts and 6 Samples from Dupuytren's contracture-derived fibroblasts were hybridized to Illumina's Sentrix Human-6 Expression Beadchip and GE Code Link arrays.

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Non-Esterified Fatty Acids of Primary Sclerosing Cholangitis (part II)

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