Fig. 3

PI3K-AKT activation drives a pro-inflammatory integrin signaling output in primary astrocytes. (A) A heat map showing the 1561 genes induced by tau PFF in primary astrocytes and their expression in control PBS-treated cells or in tau PFF treated cells that were exposed to the indicated inhibitors. n = 3 biological repeats. (B) A Venn diagram showing the relative impact of the indicated inhibitors on tau PFF-induced gene expression. The numbers indicate the number/percentage of genes whose induction was reverted by the inhibitor. (C) A paired comparison showing the relative impact of the inhibitors on tau PFF-induced gene expression. The numbers indicate the number of genes whose induction was reverted by the inhibitor. (D) A working model showing the integrin-FAK-PI3K-AKT-NFκB signaling axis that determines a pro-inflammatory response in tau PFF-treated astrocytes. (E, F) STRING biological process analysis of tau PFF-induced genes commonly regulated by FAK and PI3K (E) or those by both AKT and NFκB (F). FDR, false discovery rate. (G) The expression of selected chemokine family members in astrocytes treated with tau PFF together with the indicated inhibitors. Error bars indicate means ± SD. n = 3 biological repeats. (H) A heat map shows the relative expression of cytokines in primary astrocytes treated with tau PFF and the indicated inhibitors