Novel PPARy Modulator GED-0507-34 Levo Ameliorates Inflammation-driven Intestinal XXXX .

@entity1 @entity82 @entity4047 @entity19 @entity31 @entity1372 @entity17712 @entity13239 @entity1970 @entity1960 @entity3504 @entity2533 @entity8946 @entity30
BACKGROUND: Intestinal @entity82 is mainly associated with @entity30 and is defined as a progressive and excessive deposition of extracellular matrix components. No specific antifibrotic therapies are available. In this study, we evaluate the antifibrotic effect of a novel @entity3504 analog able to activate the peroxisome proliferator-activated receptor y, named GED-0507-34 Levo. METHODS: Colonic @entity82 was induced in 110 C57BL/6 @entity19 by 3 cycles of 2.5% (wt/vol) dextran sulfate @entity1372 administration for 6 weeks. The preventive effects of oral daily GED (30 mg  kg  d) administration were evaluated using a macroscopic and histological score and also through biological endpoints. Expression of main markers of myofibroblasts activation was determined in transforming growth factor ( @entity2533 )-stimulated intestinal fibroblasts and epithelial cells. RESULTS: GED improved macroscopic and microscopic intestinal lesions in dextran sulfate @entity1372 -treated animals and reduced the profibrotic gene expression of @entity17712 , @entity13239 , and @entity8946 by 1.48-folds (P < 0.05), 1.93-folds (P < 0.005), and 1.03-fold (P < 0.05), respectively. It reduced protein levels of main markers of @entity82 ( @entity1970 and Collagen I-II) and the main @entity2533 /Smad pathway components. GED also decreased the @entity4047 and connective tissue growth factor expression by 1.89-folds (P < 0.05) and 2.2-folds (P < 0.005), respectively. GED inhibited @entity2533 -induced activation of both fibroblast and intestinal epithelial cell lines, by regulating mRNA expression of @entity1970 and fibronectin, and restoring the @entity2533 -induced loss of intestinal epithelial cell markers. GED treatment also reduced the @entity2533 and @entity1970 expression in primary @entity1 intestinal fibroblasts from @entity31 @entity1 . CONCLUSIONS: GED ameliorates intestinal @entity82 in dextran sulfate @entity1372 -induced @entity1960 in @entity19 and regulates major profibrotic cellular and molecular mechanisms.
