ArrayExpress Uploaderarrayexpress_sidhumanTGF6 hoursTGF6 hoursTGF6 hoursTNF6 hoursTNF6 hoursTNF6 hoursTGF42 hoursTGF42 hoursTGF42 hoursTNF42 hoursTNF42 hoursTNF42 hours320904Aberrant epithelial-mesenchymal transition (EMT) is involved in　pathological processes including fibrotic disorders and cancer invasion...E-GEOD-15205/profile/8773/arrayexpressuploader212actincancercelleyegenomehyaluronanpointproteinDec.12, 2014FalseE-GEOD-15205_A-AFFY-44tgf-or-tnf-time-series-in-arpe19TGF or TNF Time series in ARPE19Sep.12, 2014Aberrant epithelial-mesenchymal transition (EMT) is involved in　pathological processes including fibrotic disorders and cancer invasion and metastasis. Alterations of the cell-extracellular matrix　(ECM) interaction also contribute to those pathological settings.　However, the functional interplay between EMT and cell-ECM　interaction is poorly understood. Here, we show that tumor necrosis factor (TNF)-α, a potent mediator of inflammation, induces　EMT-associated fibrosis in retinal pigment epithelial cells, and that this is regulated by hyaluronan (HA)-CD44-Moesin interaction. TNF-α elicits both HA synthesis and Moesin phosphorylation through protein kinase C activation, promoting binding of CD44 to the newly synthesized HA. The HA-CD44-Moesin interaction leads to cell-cell dissociation through actin remodeling and increased cellular motility associated with mesenchymal phenotype. Furthermore, we　established an in vivo model of TNF-α-induced fibrosis in the mouse eye, and the ocular fibrosis was completely suppressed in CD44-null mice. Therefore, HA production and its interaction with CD44 plays essential role in TNF-α-induced-EMT, and the interference of the complex formation can be a new strategy for the fibrotic disorders. ARPE19 cell lines were treated with TGF and TNF for 6 and 42 hour. Each experiment were repeated three times. But 1hour experiment was repeated two times. For this submission, total RNA was extracted from TGF- or TNF-treated ARPE-19 cells and differential gene expression between each time point (6 and 42 hours) was determined using genechip arrays (Affymetrix, Human Genome U133).http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-15205http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-15205/samples/