Fig. 7: LPC promotes ASIC3 activation in psoriatic inflammation.

a Relative levels of LPC molecular species increased in skin samples of Asic3^+/+ mice after the IMQ treatment. For each species, the data were normalized to that of the vehicle control. Statistical analysis used raw data as described in Supplementary Fig. 12a. F_(1,304) = 39.71, LPC (14:0): ***p = 1.3268E−7 < 0.001; LPC (16:1): ***p = 3.1771E−7 < 0.001; LPC (18:2): *p = 0.0277 < 0.05; LPC (18:3): *p = 0.0368 < 0.05; LPC (20:3): *p = 0.0285 < 0.05); multiple comparisons with Benjamini-Hochberg adjustment. b Whole-cell currents. Bath solution was changed to pH 7.4, pH 7.0 and pH 6.5 containing LPC14:0 (30 μM) or not as indicated in the horizontal bars. c Peak current density without leak subtraction in response to exposure to bath solutions of different pH before and after applications of 30 μM LPC14:0 in CHO cells transfected with mAsic3. pH 7.4: ***p = 4.1232E−5 < 0.001, n = 5; pH 7.0: **p = 0.0097 < 0.01, n = 5; pH 6.5: ***p = 0.0009 < 0.001, n = 5; two-side paired t-tests. d CGRP levels in supernatant of DRG neurons. n = 4 for each group. F_(1,36) = 260.9, pH 7.4: p = 0.7819; pH 7.0: ***p = 0.0003 < 0.001; pH 6.5: ***p = 3.7503E−7 < 0.001; pH 7.4 + LPC: ***p = 1.0722E−11 < 0.001; pH 7.0 + LPC: ***p = 9.5219E−7 < 0.001; pH 6.5 + LPC: ***p = 3.8016E−11 < 0.001; Asic3^−/− vs. Asic3^+/+; Asic3^+/+: F_(5,36) = 18.94, ^###p = 3.7748E−8 < 0.001, pH 7.4 vs. pH 7.4 + LPC; ^#p = 0.0268 < 0.05, pH 7.0 vs. pH 7.0 + LPC; ^###p = 2.2664E−5 < 0.001, pH 6.5 vs. pH 6.5 + LPC; two-way ANOVA. Representative sections (e) and quantification of epidermal thickness (f) in lesional skins after LPC treatment. Scale bar, 100 μm. F_(1,14) = 33.65, Asic3^+/+: ***p = 4.4806E−5 < 0.001, vehicle vs. LPC; Asic3^−/−: p = 0.1943, vehicle vs. LPC; two-way ANOVA. Representative Ki67 staining (g) and number of Ki67⁺ cells (h) in lesional skins. Scale bar, 100 μm. F_(1,14) = 5.187, Asic3^+/+: *p = 0.0109 < 0.05, vehicle vs. LPC; Asic3^−/−: p = 0.9617, vehicle vs. LPC; two-way ANOVA. i Psoriasis-related cytokine. IL-17: F_(1,14) = 36.89, Asic3^+/+: ***p = 3.4388E−5 < 0.001; Asic3^−/−: p = 0.1307, vehicle vs. LPC; two-way ANOVA. IL-22: F_(1,14) = 11.59, Asic3^+/+: **p = 0.0031 < 0.01; Asic3^−/−: p = 0.7313, vehicle vs. LPC_; two-way ANOVA. IL-23: F_(1,14) = 4.245, Asic3^+/+: *p = 0.0253 < 0.05; Asic3^−/−: p = 0.9937, vehicle vs. LPC; two-way ANOVA. n = 4 and 5 for the Asic3^+/+ and Asic3^−/− groups. Summary data are mean ± SEM.