Fig. 4: PI3KαH1047R increases IL-6 secretion to drive vascular dysfunction and remodeling. | Nature Communications

Fig. 4: PI3KαH1047R increases IL-6 secretion to drive vascular dysfunction and remodeling.

From: Uncovering mutation-specific morphogenic phenotypes and paracrine-mediated vessel dysfunction in a biomimetic vascularized mammary duct platform

Fig. 4

a Representative western blot and associated quantification of conditioned media from EV, ErbB2amp, and PI3KαH1047R ducts immunoblotted for human IL-6 and IL-6Rα (n = 3 western blots from three independent experiments). b Top right: Experimental schematic of endothelial vessel-conditioned media setup. Maximum intensity projection micrographs of endothelial vessels treated overnight with EV, EV+ recombinant human IL-6 (rhIL-6) (200 ng/ml), or PI3KαH1047R conditioned media; phalloidin (green), DAPI (blue). c Diffusive permeability PD (n = 4, 5, 5, 5 vessels examined across three independent experiments; one-way ANOVA with Bonferroni post test, BM + rhIL-6 vs EV + rhIL-6 *P = 0.019, BM + rhIL-6 vs PI3KαH1047R *P = 0.035, EV vs EV + rhIL-6 *P = 0.0104, EV vs PI3KαH1047R *P = 0.0205) and (d) relative cortical actin measured from vessels treated overnight with basal assay medium supplemented with 200 ng/ml rhIL-6 (BM + rhIL-6) or EV, EV + rhIL-6, or PI3KαH1047R conditioned media (n = 12, 12, 12, 12 cells examined from three vessel experiments; one-way ANOVA with Bonferroni post test, BM + rhIL-6 vs EV + rhIL-6 ***P = 1.32402e−06, BM+rhIL-6 vs PI3KαH1047R ****P = 1.08309e−08, EV vs EV + rhIL-6 ****P = 1.0819e−06, EV vs PI3KαH1047R ****P = 8.84689e−09). For all plots, values mean ± s.e.m. and all images are representative of at least three independent experiments. Source Data are provided as a Source Data file.

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