Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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DNA repair genes: Alternative transcription and gene expression at the exon level in response to the DNA damaging agent, ionizing radiation

ABSTRACT: DNA repair is an essential cellular process required to maintain genomic stability. Every cell is subjected to thousands of DNA lesions daily under normal changes in transcription. Transcription is a primary process where protein amount and function can be regulated. One aspect of the transcriptional IR response that little is known about on a whole genome basis is alternative transcription. These investigations focus on the response to IR at the exon level in human cells but also at the whole gene level. Whole genome exon arrays were utilized to comprehensively characterize radiation-induced transcriptional expression products in two human cell types, namely EBV-transformed lymphoblast and primary fibroblast cell lines. 12 human primary fibroblast cell lines and 12 primary lymphoblast cell line samples were used for two doses (0 and 10 Gy) and two time points (0 and 4hr). Additional doses ( 1 Gy, 2 Gy, 5 Gy, and 20 Gy) and time points ( 1hr, 2hr, 8hr, 24hr and 48hr) were assessed in four primary lymphoblast cell lines and four primary fibroblasts.

ORGANISM(S): Homo sapiens

SUBMITTER: Jason Li

PROVIDER: E-GEOD-41840 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Dupuytren's disease (DD) is a classic example of pathological fibrosis which results in a debilitating disorder affecting a large sector of the human population. It is characterized by excessive local proliferation of fibroblasts and over-production of collagen and other components of the extracellular matrix (ECM) in the palmar fascia. The fibrosis progressively results in contracture of elements between the palmar fascia and skin causing flexion deformity or clawing of the fingers and a severe reduction in hand function. While much is known about the pathogenesis and surgical treatment of DD, little is known about the factors that cause its onset and progression, despite many years of research. Gene expression patterns in DD patients now offers the potential to identify genes that direct the pathogenesis of DD. In this study, we used primary cultures of fibroblasts derived from excisional biopsies of fibrotic tissue from DD patients to compare the gene expression profiles on a genome-wide basis with normal control fibroblasts. Our investigations have identified genes that may be involved with DD pathogenesis including some which are directly relevant to fibrosis. In particular, these include significantly reduced expression levels of three matrix metallopeptidases (MMP1, MMP3, MMP16), follistatin, and STAT1, and significantly increased expression levels of fibroblast growth factors (FGF9, FGF11), a number of collagen genes and other ECM genes in DD patient samples. Many of these gene products are known to be involved in fibrosis, tumour formation and in the normal processes of tissue remodelling. In addition, alternative splicing was identified in some DD-associated genes. These highly sensitive genomic investigations provide new insight into the molecular mechanisms that may underpin the development and progression of DD. Four exon arrays of DD primary fibroblasts derived from fibrotic tissue were compared to fibroblasts derived from skin punch biopsies from individuals who did not show DD symptoms.

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DNA repair genes: Alternative transcription and gene expression at the exon level in response to the DNA damaging agent, ionizing radiation

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