Fig. 8: ACSS2 inhibitor suppressed H3K9cr-mediated IL-1β expression, cellular senescence, and M1 macrophage markers as well as alleviated kidney fibrosis in vivo. | Nature Communications

Fig. 8: ACSS2 inhibitor suppressed H3K9cr-mediated IL-1β expression, cellular senescence, and M1 macrophage markers as well as alleviated kidney fibrosis in vivo.

From: Inhibition of ACSS2-mediated histone crotonylation alleviates kidney fibrosis via IL-1β-dependent macrophage activation and tubular cell senescence

Fig. 8: ACSS2 inhibitor suppressed H3K9cr-mediated IL-1β expression, cellular senescence, and M1 macrophage markers as well as alleviated kidney fibrosis in vivo.The alternative text for this image may have been generated using AI.

A Treatment strategy of ACSS2 inhibitor for mice. B Protein level of H3K9cr, H3K9ac, and H3 and quantification of these immunoblots in whole kidney lysates of UUO mice treated with or without ACSS2 inhibitor (n = 3 per group, control vs. UUO: p = 0.0068, UUO vs. UUO + ACSS2 inhibitor: p = 0.0051). C Representative images of H&E (n = 6 per group, Scale bar: 100 μm), Sirus red (n = 3 per group, Scale bar: 100 μm), and IF staining α-SMA (green), COL6 (green) and DAPI (blue) in UUO mice treated with or without ACSS2 inhibitor (n = 3 per group, Scale bar: 20 μm). D Quantitative analysis of α-SMA and COL6 IF staining in UUO mice treated with or without ACSS2 inhibitor (n = 3 per group, control vs. UUO: p = 0.0014 for α-SMA, p = 0.0008 for COL6; UUO vs. UUO + ACSS2 inhibitor: p = 0.0254 for α-SMA, p = 0.0005 for COL6). E FN1, COL6, α-SMA and GAPDH immunoblotting in the whole kidney lysates of UUO mice treated with or without ACSS2 inhibitor (n = 3 per group). F mRNA levels of IL-1β in whole kidney lysates of UUO mice treated with or without ACSS2 inhibitor (the number for control and UUO group is 6, the number for ACSS2 inhibitor and UUO + ACSS2 inhibitor group is 4; control vs UUO: p = 0.0016, UUO vs UUO + ACSS2 inhibitor: p = 0.04494). G SA-β-gal staining of control, UUO fibrotic mice, and UUO mice treated with ACSS2 inhibitor (n = 3 per group). Scale bar: upper panels: 100 μm; lower panels:50 μm. H mRNA levels of Cd86, P53, Mcp1, Il6 and Tnf-α in whole kidney lysates of control, UUO fibrotic mice and UUO mice treated with ACSS2 inhibitor (number for control and UUO group is 6, number for ACSS2 inhibitor and UUO + ACSS2 inhibitor group is 4; control vs. UUO: p < 0.0001 for Cd86, p < 0.0001 for P53, p < 0.0001 for Mcp-1, p = 0.0005 for il6, p < 0.0001 for Tnf-α; UUO vs. UUO + ACSS2 inhibitor: p = 0.0136 for Cd86, p = 0.0004 for P53, p = 0.0043 for Mcp-1, p = 0.0056 for il6, p < 0.0001 for Tnf-α). Ctrl Control, UUO unilateral ureteric obstruction. Data shown are means ± SEM. Statistical analysis by one-way ANOVA with Tukey’s post hoc test. *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001.

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