G Almounajed | PubMed Health

PubMed1996

Newer aspects of the irritable bowel syndrome.

IBS is a challenging, functional GI disorder that affects many individuals around the world. Early life experiences, the biologic nature of the condition, and the psychosocial milieu interact to affect the severity and outcome of symptoms. Most people do not seek medical attention for their GI symptoms, or they require intermittent, limited medical therapy and assurance from their physician. Fewer patients, but still a significant number, demand frequent interaction with their physician, who may select pharmacotherapy or psychological and behavioral treatments to control symptoms, depending on the severity. A biopsychosocial approach with attention to the patient-doctor relationship is recommended as the basis for treatment.

Colonic Diseases, Functional↗

PubMed1995

Sp1 binding activity increases in activated Ito cells.

Ito cells are the primary cell type in the liver responsible for increased type I collagen production observed during fibrogenesis. After a fibrogenic stimulus, Ito cells change from their normal quiescent state to an activated state. In this study, we examined the expression of the alpha 1(I) collagen gene in Ito cells that were freshly isolated from normal rat liver (quiescent) and Ito cells that were activated by culture on plastic. Northern blots showed that alpha 1(I) collagen messenger RNA levels were low in freshly isolated Ito cells and Ito cells cultured on plastic for up to 4 days, but were induced after 7 days in culture. To determine the location of important transcriptional regulatory elements within the 5'-flanking region of the alpha 1(I) collagen gene, transient transfections using various portions of the alpha 1(I) collagen gene promoter linked to the luciferase gene were performed in cultured Ito cells. As in fibroblast cells, only 220 base pairs (bp) of immediate 5'-flanking sequence of the collagen alpha 1(I) gene was necessary for efficient expression of the reporter gene. Deoxyribonuclease I footprinting analysis and mobility shift assays showed dramatic differences in the DNA binding proteins that interact with the 220 base pair promoter region of the alpha 1(I) collagen gene between freshly isolated and activated Ito cells. Sp1 binding activity was greatly increased in activated Ito cells, as was binding activity for CCAAT binding factor (CBF), a transcription factor previously shown to interact with the alpha 2(I) collagen gene promoter. The increased Sp1 binding activity to the alpha 1(I) collagen gene promoter involves a posttranscriptional event, as shown by Northern and Western blots. Therefore, we show that activated Ito cells have a different pattern of transcription factor binding activity interacting with the alpha 1(I) collagen gene promoter compared with quiescent Ito cells, including increased Sp1 binding activity, and that this may contribute to the increase in alpha 1(I) collagen gene expression during fibrosis.

Animals↗