Fig. 3: Soluble tau aggregates induce senescence/SASP in primary human brain microvascular endothelial cells. | Nature Communications

Fig. 3: Soluble tau aggregates induce senescence/SASP in primary human brain microvascular endothelial cells.

From: Soluble pathogenic tau enters brain vascular endothelial cells and drives cellular senescence and brain microvascular dysfunction in a mouse model of tauopathy

Fig. 3

A–C Soluble tau aggregates increase cell and nuclear size in primary human brain microvascular endothelial cells (HBEC). A Representative images of HBEC treated with recombinant human cytokeratin-8 (KRT8), monomeric tau protein (M. Tau), soluble tau aggregates (O.Tau), or vehicle (Control). B Quantitative analyses of cell size from data shown in A. (F(3,21)=5.391, ANOVA, p = 0.0065; Control vs. O. Tau, *, p < 0.05, M.Tau vs. O. Tau #. p < 0.05 by Tukey’s. Control, n = 8; KRT8, n = 6; M. Tau, n = 4, O.Tau, n = 7 biologically independent samples examined over 2 independent experiments. Data are means ± SEM. C Nuclear area (H = 7.989, p = 0.046; Control vs. O. Tau, *p = 0.025, Control vs. M.Tau, n.s., p > 0.999 by Dunn’s. Control, n = 8; KRT8, n = 6; M. Tau, n = 4, O.Tau, n = 7 biologically independent samples examined over 2 independent experiments. Data are representative images and means ± SEM. D–F Soluble tau aggregates trigger cell cycle arrest in HBEC. D Quantitative real-time PCR (qRT-PCR) measurements of mRNA abundance for cyclin dependent kinase inhibitor 2 A (Cdkn2a, (F(3,22)=5.264, ANOVA, p = 0.007, Control vs. O. Tau, **, p < 0.01, from Tukey’s. Control, n = 16; KRT8, n = 3; M. Tau, n = 4, O.Tau, n = 3 biologically independent samples examined over 7 independent experiments. E Cyclin dependent kinase inhibitor 1 A (CDKN1A, F(3,23)=7.545, ANOVA, p = 0.0011, Control vs. O. Tau, ***p < 0.001; M. Tau vs. O.Tau, *p < 0.05; KRT8 vs. O. Tau, **p < 0.01 from Tukey’s. Control, n = 16; KRT8, n = 4; M. Tau, n = 4, O.Tau, n = 3 biologically independent samples examined over 7 independent experiments). F Tumor protein 53 (Tp53, (F(3,23) = 3.050, ANOVA, p = 0.049, KRT8 vs. O. Tau, *p < 0.05 by Tukey’s. Control, n = 16; KRT8, n = 4; M. Tau, n = 4, O.Tau, n = 3 biologically independent samples examined over 7 independent experiments). G–K Soluble tau aggregates promote expression of the senescence-associated secretory phenotype in HBEC. G Interleukin 6 (IL-6, F(3,22) = 147.7, ANOVA, p < 0.0001. Control vs. O. Tau, ****p < 0.0001; Control vs. M. Tau, ****p < 0.0001; M. Tau vs. O. Tau, ****p < 0.0001 by Holm-Sidak’s. Control, n = 16; KRT8, n = 4; M. Tau, n = 4, O.Tau, n = 2 biologically independent samples examined over 7 independent experiments). H Interleukin 1β (IL-1β, H = 16.49, Kruskal–Wallis, p = 0.0009. Control vs. O. Tau, *p < 0.05; Control vs. M. Tau, **p < 0.01. Control, n = 15; KRT8, n = 4; M. Tau, n = 4, O.Tau, n = 4 biologically independent samples examined over 7 independent experiments). I Tumor necrosis factor (TNF, F(3,21) = 14.85, ANOVA, p < 0.0001. Control vs. O. Tau, ****p < 0.0001; M. Tau vs. O. Tau, ****p < 0.0001 by Dunn’s. Control, n = 15; KRT8, n = 4; M. Tau, n = 4, O.Tau, n = 2 biologically independent samples examined over seven independent experiments). J Monocyte chemoattractant protein-1(MCP-1, F(3,22) = 12.44, ANOVA, p < 0.0001. Control vs. O. Tau, *, p < 0.05; Control vs. M. Tau, ***p < 0.01 by Holm–Sidak’s. Control, n = 15; KRT8, n = 4; M. Tau, n = 4, O.Tau, n = 3 biologically independent samples examined over seven independent experiments). K Plasminogen-activator inhibitor-1 (PAI-1, F(3,22) = 4.173, ANOVA, p = 0.018. Control vs. O. Tau, *p < 0.05 by Holm-Sidak’s. Control, n = 15; KRT8, n = 4; M. Tau, n = 4, O.Tau, n = 3 biologically independent samples examined over seven independent experiments). Data are representative images and means ± SEM. For post-hoc analyses, lack of a specific P value in the legend reflects the information reported by GraphPad Prism Version 9.4.0.

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