Fig. 1: PCSK9 silencing enhances cGAS-STING activation.
a Schematic illustrating the aim and strategy of the clinical data analysis. b–g Correlations between PCSK9 and indicated innate immune signaling-related genes. Shown are mRNA levels of b PCSK9 and IFN-β, c PCSK9 and ISG20, d PCSK9 and STING, e PCSK9 and MAVS, f PCSK9 and IL-6, and g PCSK9 and IL-1β (GEO dataset: GSE15781, n = 42 patients). h, i BMDCs were incubated with siPCSK9 (h) or siCtrl (i) and/or different concentrations of Mn2+. After 24 h, IFN-β secretion was quantified by ELISA (n = 3 independent experiments). j, k Dose-response curves of the IFN-β response in BMDCs after siPCSK9 or siCtrl treatment (n = 3 independent experiments). The EC50 values are shown for the indicated formulations. l Raw264.7 ISG luciferase reporter cells were exposed to Mn2+(50 μM), and/or siPCSK9 (7.5 µg/ml) for 24 h before measuring the luciferase signal. m, THP1 ISG luciferase reporter cells were exposed to Mn2+ (50 μM), and/or siPCSK9/siCtrl (7.5 µg/ml) for 24 h before measuring the luciferase signal (n = 3 independent experiments). n THP1-Luica ISG reporter cells, were exposed to c-di-AMP (1 μM), and/or siPCSK9/siCtrl (7.5 µg/ml) for 24 h before measuring the luciferase signal (n = 3 independent experiments). o THP1-Lucia ISG reporter cells were exposed to cGAMP (1 μM), and/or siPCSK9/siCtrl (7.5 µg/ml) for 24 h before measuring the luciferase signal (n = 3 independent experiments). Data represent mean ± SD. Data were analyzed by one-way analysis of variance (ANOVA) with Tukey’s multiple comparisons post-test (l–o) or two-way ANOVA with Bonferroni’s multiple comparisons post-test (j, k). Source data are provided as a Source Data file. Panel (a) was created in BioRender. Kuai, R. (2025) https://BioRender.com/28bogc8.
