Journal: Brain Pathology

Article Title: Complement C3a induces axonal hypomyelination in the periventricular white matter through activation of WNT/β‐catenin signal pathway in septic neonatal rats experimentally induced by lipopolysaccharide

doi: 10.1111/bpa.12798

Figure Lengend Snippet: Primary antibodies used in experiments.

Article Snippet: To investigate whether C3a administration would activate WNT/β‐catenin pathway in the OPCs, XAV‐939 (a selective inhibitor against Wnt/β‐catenin‐mediated transcription by tankyrase1/2) (MedChemExpress, Cat. No. HY‐15147) was used to reverse the effect of C3a administration on the differentiation and maturation of OPCs.

Techniques: Concentration Assay

Journal: Brain Pathology

Article Title: Complement C3a induces axonal hypomyelination in the periventricular white matter through activation of WNT/β‐catenin signal pathway in septic neonatal rats experimentally induced by lipopolysaccharide

doi: 10.1111/bpa.12798

Figure Lengend Snippet: C3a inhibits the differentiation and maturation of OPCs in vitro. Immunofluorescence images of cultured OPCs showing the expression of MBP (A–D, green), NG2 (E–H, green) and DAPI (blue) at 4 days after the C3a, C3a + C3aRa and C3aRa treatment when compared with the corresponding control at the magnification of ×40 (n = 5). Panel I shows the immunoreactive bands of PLP (26 kDa), MBP (33 kDa), CNPase (47 kDa), MAG (69 kDa), NG2 (251 kDa), CC1 (310 kDa), Olig1 (26 kDa), Olig2 (37 kDa), SOX10 (49 kDa) and β‐actin (42 kDa) after C3a administration or C3a + C3aRa treatment or C3aRa treatment and the corresponding control (n = 6). Bar graphs (J–R) show the optical density of protein expression shown in I (n = 6). (S, T) Bar graphs show the percentage of MBP+/DAPI+ and NG2+/DAPI+ cells at 4 d after the C3a, C3a + C3aRa and C3aRa treatment when compared with the corresponding control (n = 5). For statistical analysis, one‐way ANOVA with Tukey's post hoc test was used for J–T and presented as the mean ± standard error of measurement (SEM). Scale bars: 20 μm. *P < 0.05, **P < 0.01.

Article Snippet: To investigate whether C3a administration would activate WNT/β‐catenin pathway in the OPCs, XAV‐939 (a selective inhibitor against Wnt/β‐catenin‐mediated transcription by tankyrase1/2) (MedChemExpress, Cat. No. HY‐15147) was used to reverse the effect of C3a administration on the differentiation and maturation of OPCs.

Techniques: In Vitro, Immunofluorescence, Cell Culture, Expressing, Control

Journal: Brain Pathology

Article Title: Complement C3a induces axonal hypomyelination in the periventricular white matter through activation of WNT/β‐catenin signal pathway in septic neonatal rats experimentally induced by lipopolysaccharide

doi: 10.1111/bpa.12798

Figure Lengend Snippet: C3a delays the differentiation and maturation of OPCs in vitro by activating the WNT/β‐catenin pathway. C3a administration activates the WNT/β‐catenin pathway in primary culture of OPCs. Panel A shows TCF4, β‐catenin, β‐catenin phosphorylation and AXIN2 immunoreactive bands after C3a treatment for 15 minutes, 30 minutes, 1, 2, and 4 h and the corresponding control (n = 6). Bar graphs (B–E) show the optical density of protein expression in A (n = 6). XAV939, an inhibitor of WNT/β‐catenin pathway, reverses the effect of C3a in primary culture of OPCs. Panel F shows the immunoreactive bands of PLP (26 kDa), MBP (33 kDa), CNPase (47 kDa), MAG (69 kDa), NG2 (251 kDa), CC1 (310 kDa), Olig1 (26 kDa), Olig2 (37 kDa), SOX10 (49 kDa) and β‐actin (42 kDa) after C3a, C3a + C3aRa, C3a + XAV939, XAV939 treatment and the corresponding control (n = 6). Bar graphs (G–O) show the optical density of protein expression in I (n = 6). For statistical analysis, one‐way ANOVA with Tukey's post hoc test was used for B–E and G–O and presented as the mean ± standard error of measurement (SEM). Scale bars: 20 μm. *P < 0.05, **P < 0.01.

Article Snippet: To investigate whether C3a administration would activate WNT/β‐catenin pathway in the OPCs, XAV‐939 (a selective inhibitor against Wnt/β‐catenin‐mediated transcription by tankyrase1/2) (MedChemExpress, Cat. No. HY‐15147) was used to reverse the effect of C3a administration on the differentiation and maturation of OPCs.

Techniques: In Vitro, Phospho-proteomics, Control, Expressing

Journal: Brain Pathology

Article Title: Complement C3a induces axonal hypomyelination in the periventricular white matter through activation of WNT/β‐catenin signal pathway in septic neonatal rats experimentally induced by lipopolysaccharide

doi: 10.1111/bpa.12798

Figure Lengend Snippet: Table of Contents Image (TOCI): A sketch map demonstrates the cellular and molecular mechanism associated with PWMD in the septic neonatal rats. Microglia and astrocyte are activated in the PWM after intraperitoneal injection of LPS and release massive amounts of C3a and IL‐1β. Then they will bind to their receptors (C3aR and IL‐1R1) on the OLs and may activate AKT signaling pathway. It will inhibit GSK3β, allowing β‐catenin cytoplasmic accumulation and binding to TCF4 in the nucleus for nuclear translocation to active WNT/β‐catenin signaling pathway. It can lead to the delay of maturation or differentiation of OPCs through inhibiting the differentiation transcription factor of OPCs. This would contribute to axonal hypomyelination in the PWM in the experimental induced septic neonatal rats. XAV‐939, a selective inhibitor of WNT/β‐catenin signaling pathway, which may indirectly stabilize Axin2 through Tankyrase1/2, can promote the maturation or differentiation of OPCs in vitro.

Article Snippet: To investigate whether C3a administration would activate WNT/β‐catenin pathway in the OPCs, XAV‐939 (a selective inhibitor against Wnt/β‐catenin‐mediated transcription by tankyrase1/2) (MedChemExpress, Cat. No. HY‐15147) was used to reverse the effect of C3a administration on the differentiation and maturation of OPCs.

Techniques: Injection, Binding Assay, Translocation Assay, In Vitro