PPM1K Antibody - #DF4348

Fig. 2 Conditional knockout of PP2Cm in DRG neurons induces pain hypersensitivity a, Representative cartoons of pAAV9-hSyn-(Cre) injection. Intrathecal injection of pAAV9-hSyn-Cre or pAAV9-hSyn into male and female PP2Cmfl/fl mice resulted in the generation of PP2Cm-cKO and PP2Cm-ctrl mice. b, Representative immunoblots of PP2Cm in the L4-L5 DRGs on day 21 post-injection in PP2Cm-cKO and PP2Cm-ctrl mice of both sexes. male n = 3 experimental repeats (6 mice)/group, female n = 3 experimental repeats (6 mice)/group. c-e, Mechanical withdrawal thresholds (c), withdrawal latencies to heat (d) and cold stimulus (e) in PP2Cm-cKO and PP2Cm-ctrl mice. n = 10 mice/group, both sexes. f, BCAA concentrations in the L4-L5 DRGs of PP2Cm-cKO and PP2Cm-ctrl mice. n = 5 mice/group, both sexes. g-i, Mechanical withdrawal thresholds (g), withdrawal latencies to heat (h) and cold stimulus (i) in PP2Cm-cKO mice with or without BT2 supplementation after 7 consecutive days, PP2Cm-cKO + Vehicle vs. PP2Cm-cKO + BT2. n = 6 mice/group, both sexes. j, BCAA concentrations in the L4-L5 DRGs of PP2Cm-cKO + Vehicle and PP2Cm-cKO + BT2 mice. n = 6 mice/group, both sexes. Data are shown as the mean ± SEM. Statistical tests used were unpaired two-tailed Student’s t-test (c-e, g-i), one-way ANOVA with Tukey’s multiple comparisons test (b), and two-way repeated-measures ANOVA with Bonferroni’s post hoc test (f, j). *p 

Fig. 4 Inhibiting the CCL5/CCR5 signaling pathway attenuates hyperalgesia in DRG PP2Cm-deficient mice a, Quantification for release of CCL5 in the L4-L5 DRGs of PP2Cm-ctrl and PP2Cm-cKO mice, as detected by ELISA. n = 4 mice/group. b, Illustrative cartoon depicting the intrathecal administration of an anti-CCL5 neutralizing antibody. c, Quantification for release of CCL5 in the L4-L5 DRGs of PP2Cm-cKO + IgG, PP2Cm-cKO + anti-CCL5 1d and PP2Cm-cKO + anti-CCL5 3d mice. n = 4 mice/group. d-f, Mechanical withdrawal thresholds (d), withdrawal latencies to heat (e) and cold stimulus (f) on day 0 (baseline, BL), 1, and 3 post-injection in PP2Cm-cKO mice treated with IgG or anti-CCL5 neutralizing antibody. n = 5–6 mice/group. g, The L4-L5 DRGs from PP2Cm-ctrl and PP2Cm-cKO mice were double stained with PP2Cm (green) and CCR5 (red). The corner image in white square is the zoomed-in image of the area in the smaller white square. Scale bar: 20 μm. h, i, Fluorescent quantifications for PP2Cm (h) and CCR5 (i) in DRG sections from PP2Cm-ctrl and PP2Cm-cKO mice. n = 3 sections from 3 mice/group. j, A representative cartoon illustrating the intrathecal injection of CCR5 antagonist maraviroc or Ccr5 small interfering RNA (siCcr5). k-m, Mechanical withdrawal thresholds (k), withdrawal latencies to heat (l) and cold stimulus (m) at BL, 1 h, and 24 h post-injection in PP2Cm-cKO mice treated with Vehicle or maraviroc. n = 6 mice/group. n, The mRNA levels of Ccr5 in the L4-L5 DRGs from PP2Cm-cKO + siCtrl, PP2Cm-cKO + siCcr5 2d, and PP2Cm-cKO + siCcr5 8d mice (to β-actin). n = 3 experimental repeats (6 mice)/group. o-q, Mechanical withdrawal thresholds (o), withdrawal latencies to heat (p) and cold stimulus (q) at BL, 2d, and 8d post-injection in PP2Cm-cKO mice treated with siCtrl or siCcr5. n = 5–6 mice/group. Data are shown as the mean ± SEM. Statistical tests used were unpaired two-tailed Student’s t-test (a, h, i), one-way ANOVA with Tukey’s multiple comparisons test (c, n), and two-way repeated-measures ANOVA with Bonferroni’s post hoc test (d-f, k-m, o-q). *p