However, much remains to be done in automatic extraction of experimental evidence of DDI from text

exposed to both types of PSC-CCMs. Hyperglycemia exposure decreased the amount of pAkt and pAkt in T3M4 cells, in contrast, the exposure of cancer cells to PSC-CCM increased the amount of pAkt. Both receptors of CXCL12, the CXCR4 and the CXCR7 were expressed on the T3M4 cells. T3M4 cells exposed directly to hyperglycemia or to different conditioned PSC culture media expressed increased amount of CXCR4, mostly after treatment of T3M4 cells with the culture medium of PSCs that were previously exposed to CHG. In contrast, we found no alteration in the CXCR7 protein expression on T3M4 cells after different treatments. WB results with the relative density values are indicated on Fig 5C. Only a modest, non-significant increase in c-FOS and in FAK proteins were found in T3M4 cells exposed to both types of PSC-CCMs nor the protein expressions of PTEN and PKC were significantly altered in the T3M4 cells after different treatments. Discussion The epidemiologic link between DM and PaC motivated this line of research. We hypothesized that CHG might induce trans-differentiation of PSCs and contribute to the development and progression of pancreatic fibrosis and cancer. The hypothesis was assessed using human, immortalized RLT-PSC cell line in a unique experimental setup. A variety of PSC activating factors were previously identified, but the role of chronic hyperglycemia in PSC activation has not been investigated to date. Previous studies reported a hyperglycemia induced activation of rat PSCs, but only up to 72 hours and without a genome-wide approach. We found that human PSCs increased the cytoplasmic SMA micro-filament formation and tended to increase major ECM protein constituents upon exposure to CHG. The genome-wide microarray approach was used to assess the glucose-induced alterations in mRNA expression patterns. The MetaCore pathway database software was used for preliminary identification of diabetes associated pathways, after the selection of the top 300 differentially expressed genes. Each PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19699128 molecular pathway was the result of the integration of multiple sets of genes with altered mRNA expressions in the microarray. Subsequently we validated the mRNA expressions for a selected set of genes using realtime PCR. Key signaling molecules were then assessed at protein level in PSCs. The phosphorylation of p38 was the most significant change in PSCs PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19696906 after exposure to CHG. We could not provide a clear-cut upstream pathway for hyperglycemia induced increased phosphorylation of p38 in PSCs, however similar results were reported in cultured human peritoneal mesothelial cells exposed to high glucose concentration, indicating that the p38 MAPK activation played a role in fibrosis development. Activation of p38 pathway was also essential in the high glucose concentration induced epithelial-mesenchymal transition of cultured human renal tubular epithelial cells and EMT of acini in the pancreas may contribute to the ultimate PSC population. In addition, the p38 pathway is activated during gluco-lipotoxicity induced apoptosis in insulin secreting INS-1 cells. SP1 was selected for WB analysis due to that the proximal promoter of JW-55 CXCL12 is occupied by six putative SP1 binding motifs as confirmed by functional methods 10 / 18 Effect of Hyperglycemia on Pancreatic Stellate and Cancer Cells 11 / 18 Effect of Hyperglycemia on Pancreatic Stellate and Cancer Cells Fig 5. Proliferation and migration assays of T3M4 cells and the Western blot analyses of key signalin