Project description:Expression of LIX1L is increased in fibrotic livers and associated with liver fibrosis stage. We investigated whether increased LIX1L expression promotes Hepatic stellate cells (HSCs) activation and liver fibrosis progression by interacting with Chemokine signaling pathway.
Project description:Fibrosis is a leading cause of deaths in industrialized countries and has no effective therapy. We demonstrated that blockade of OX40L prevented inflammation-driven fibrosis affecting the skin and the lungs and promotes regression of established dermal fibrosis in different murine models. To characterize the pathways involved in the protection of skin fibrosis and affected by OX40L blocking, we used microarrays and identified distinct genes differentially expressed between ox40l+/+ and ox40l-/- in the bleomycin-induced dermal fibrosis mouse model. Total RNA were extracted from lesional skin samples of 3 ox40l+/+ and 4 ox40l-/- male mice aged 9 weeks treated with bleomycin for 3 weeks, and were hybridized on Affymetrix microarrays.
Project description:Dietary fat consumption during rapid mammary gland developing period such as peri-pubertal maturation or pregnancy increases the risk for breast cancer. However, the molecular mechanism underlying this observation is not well elucidated. To provide mechanistic insight, we examined gene expression profile in mouse mammary epithelial cells (MMECs) exposed to high-fat diet (HFD) or control diet (CD). Trp53-/- female mice were treated with experimental diets for 5 weeks during the peri-puberty period (3 to 8 weeks of age). This treatment induced insignificant difference in body weight between mice exposed to HFD and CD. Gene Set Enrichment Analysis (GSEA) predicted elevated expression of c-Myc target genes when exposed to HFD. Consistently, we detected marked elevation of c-Myc protein and prolongation of its half-life in MMECs exposed to HFD suggesting that HFD increased its stability. Additionally, we observed increased phosphorylation at c-MycS62 with concomitant increase in ERK phosphorylation. HFD rendered Trp53-/- MMECs more colonogenic and spherogenic, which was antagonized by a c-Myc inhibitor. Oleic acid the main fatty acid constituent of the HFD and TAK-875 an agonist for G protein-coupled receptor 40 (a receptor for oleic acid) as well enhanced c-Myc stabilization and MMECs proliferation. Collectively, these data suggest that HFD exerts its effect on MMECs through the stabilization of an oncoprotein, deciphering a novel mechanism whereby dietary fat promotes mammary carcinogenesis.