Fig 1: Decorin inhibits Nf1-OPG formation.a Decorin (800 pg/ml) attenuated activated TCM (act-Tm)-mediated microglia Ccl5 production (n = 3). Two-tailed Student’s t test. Exact P values are indicated within each panel (ns, not significant). b Decorin reduces microglia Ccl5 production in response to Ccl4 exposure (6 ng/ml) over a physiologic dose range in vitro (n = 4). One-way ANOVA with Bonferroni post hoc correction. Data are presented as the means ± SEM. c TCM (activated T cell-conditioned media) induced microglial Ccl5 production was significantly attenuated by decorin. The addition of Dcn with CCR5 has the greatest inhibition similar to the combination of CCR5 and CCR8 inhibitors (n = 6). One-way ANOVA with Bonferroni post hoc correction. Data are presented as the means ± SEM. d Schematic representation of decorin binding to the CCR8 receptor on microglia, culminating is reduced microglial Ccl5 production by inhibiting NF?B activation. e Schematic representation of decorin treatment of Nf1OPG mice. Nf1OPG mice were treated between 4 and 6 weeks of age with decorin, while control Nf1OPG mice received PBS only. Isolated optic nerves were analyzed at 12 weeks of age. f Decorin treatment has no change on optic nerve volume, but (g) decreased proliferation (%Ki67+ cells) of Nf1OPG mice relative to the vehicle-treated Nf1OPG controls (PBS, n = 8, Decorin, n = 8). No difference in microglia (%Iba1+ cells) or T cell (CD3+ cells) content was observed between decorin-treated mice and their respective controls. Two-tailed Student’s t test (ns, not significant). g Scale bars, 40 µm. From left to right in each panel: a P = 0.0134, b P < 0.0001, P = 0.0035; c P < 0.0001, ns, P = 0.0086, ns; f ns; g P = 0.0010, ns, ns.
Fig 2: Decorin is significantly increased in CSF of AppNL-F/NL-F mice and a + t- preclinical AD subjects. a Venn diagrams showing the number of proteins with expression levels above one and below one and b significantly changed proteins (p < 0.05) in the CSF of AppNL-F/NL-F mice and NC/MCI/AD human cohorts from abnormal-amyloid/normal-tau subjects. Among those significantly changed proteins, ECM protein decorin is the only significantly upregulated protein in NC subjects and AppNL-F/NL-F mice. c The gene names of significantly upregulated and downregulated proteins in both AppNL-F/NL-F mouse and human CSF. d Venn diagrams showing the number of proteins with expression levels above one and below one and e significantly changed proteins (p < 0.05) in the CSF of AppNL-G-F/NL-G-F mice and NC/MCI/AD human cohorts from abnormal-amyloid/normal-tau subjects. f The gene names of significantly upregulated and downregulated proteins in both AppNL-G-F/NL-G-F mouse and human CSF. # denotes ECM-associated proteins. NC normal cognition, MCI mild cognitive impairment, AD mild to moderate AD-type dementia, CSF cerebrospinal fluid, DCN decorin
Fig 3: Increased CSF-decorin in three different mouse models of Aß pathology. a, b Immunostaining and quantification of decorin in the ChP. Scale bars, 100 µm. (n = 4). c Double immunostaining of DCN and PV or d SRIF in mouse hippocampus. e Quantification of decorin-positive cell-type distribution. Scale bars, 500 µm. (n = 3). f, g Immunostaining and quantification of decorin in the hippocampus. Scale bars, 500 µm. (n = 4). h Mouse CSF-decorin levels in three months old (n = 5), i 13 months old (n = 4–5), j 18 months old (n = 3–5) mice were measured by ELISA and quantified. k CSF-decorin levels in AppNL-F/NL-F mice of different ages were measured and quantified. (n = 3–5). l Decorin levels in Aß42 treated mouse primary neurons and (m) were quantified (n = 4). n Quantification of decorin levels in conditioned media. (n = 8). Data in (b, g–k) were analyzed by one-way ANOVA followed by Dunnett’s multiple comparisons test. Data in (m, n) were analyzed by student’s t-test. Data in (e) were analyzed by two-way ANOVA followed by Tukey’s post hoc test. Data are represented as mean ± SEM; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. DCN decorin, PV parvalbumin, SRIF somatotropin release-inhibiting factor, PN pyramidal neurons, ns not significant
Fig 4: Asthma-induced T cell decorin inhibits microglia Ccl5 level.a Heatmap showing differential gene expression in CD3+ T cells from PBS- versus OVA-treated Nf1OPG mice (n = 5). b Top transcripts increased in T cells from OVA-, relative to PBS-treated, Nf1OPG mice calculated with DESeq2 were filtered for only those genes with P values = 0.01, false discovery rates = 0.05, and log fold changes greater or equal to ±5. P values, false discovery rate (FDR), and fold changes are shown in a tabular form. c Increased Dcn gene expression was detected in both splenic CD4+ and CD8+ T cells from OVA-treated Nf1OPG mice relative to PBS-treated controls. Data are presented as the means ± SEM of n = 3 independent biological samples. d DCN RNA expression was increased in CD4+ and CD8+ T cells from patients with non-steroid-dependent asthma (n = 4) relative to healthy controls (n = 6; GSE31773). Two-tailed Student’s t test. Exact p values are indicated within each panel. e Similar levels of Dcn mRNA expression were observed in T cells from the blood (n = 5), optic nerves (n = 5), and cervical lymph nodes (n = 5) in Nf1OPG mice treated with OVA. Data are presented as the means ± SEM of n = 5 independent biological samples. One-way ANOVA with Bonferroni post hoc correction. f Increased Dcn levels were detected in CD3+ T cell-conditioned medium (TCM) from OVA-treated Nf1OPG mice relative to PBS-treated controls by ELISA. Two-tailed Student’s t test. Exact P values are indicated within the panel. Data are presented as the means ± SEM of n = 3 independent biological samples. From left to right in each panel: c P = 0.0006, P = 0.0002; d P = 0.0007, P = 0.0032; e ns; f P = 0.0003.
Fig 5: CSF-decorin positively correlates with CSF-Aß42 in a + t- preclinical AD and predicts a subtype of AD. a CSF-DCN levels in a-t- healthy (n = 82) and a + t- subjects with preclinical AD (n = 36), MCI (n = 24), AD (n = 17), and a + t + AD (n = 62). (*p < 0.05 as compared to a-t- healthy). b Correlations of CSF-DCN and CSF-Aß42, c CSF-DCN and CSF-t-tau, d CSF-DCN and CSF-p-tau in a-t- healthy and a + t- preclinical AD subjects. The regression coefficients (Beta) and p-values are displayed. (*p < 0.05, **p < 0.01, ****p < 0.0001). e Hypothetical curve showing CSF-DCN alteration from a-t- healthy subjects to a + t- preclinical AD, MCI, AD and a + t + AD subjects and its correlation with CSF-Aß42 and CSF-tau levels. f Receiver operating characteristic (ROC) analysis was performed in a + t- preclinical AD (n = 36) versus healthy control (n = 82) and revealed an area under the ROC Curve (AUC) (95% confidence interval (CI)) = 0.61 (0.50, 0.73) (p = 0.058) for CSF-DCN levels. g ROC curve was performed in a subtype classified by as innate immune activation (n = 71) versus healthy control (n = 82) and revealed an AUC (95% CI) = 0.70 (0.62, 0.79) (p = 1.73 × 10–6) for CSF-DCN levels. Data in (a) were analyzed by one-way ANOVA followed by Tukey’s multiple comparisons test. Data are represented as mean ± SEM. DCN: decorin
Supplier Page from Abcam for Mouse Decorin ELISA Kit (DCN)