Journal: Journal of Bone Oncology
Article Title: Cav3.2 T-Type calcium channels downregulation attenuates bone cancer pain induced by inhibiting IGF-1/HIF-1α signaling pathway in the rat spinal cord
doi: 10.1016/j.jbo.2023.100495
Figure Lengend Snippet: Increased expression of IGF-1 and IGF-1R and inhibition of IGF-1R reverses the upregulation of Cav3.2 and alleviates pain hypersensitivity in BCP rats. (A) IGF-1 expression increased in the dorsal horn of the spinal cord from day 14 to day 21 in BCP rats compared to sham-operation rats. Upper: representative image of Western blot bands in ipsilateral side of the lumbar enlargement lysates; lower: statistical analysis of protein expression. n = 7. * p < 0.05, two-way ANOVA with Bonferroni’s post hoc test. (B) IGF-1R expression increased in the dorsal horn of the spinal cord from day 3 to day 21 in BCP rats compared to sham-operation rats. Upper: representative image of Western blot bands in ipsilateral side of the lumbar enlargement lysates; lower: statistical analysis of protein expression. n = 7. * p < 0.05, two-way ANOVA with Bonferroni’s post hoc test. (C) Representative immunofluorescent images 14 days after BCP and sham rats. (D) Quantification showed that the percentage of Cav3.2 and IGF-1R colabeled cells increased in the BCP group compared to the sham group. Scale bar = 100 or 50 μm (the partial lumbar enlargements). n = 4. * p < 0.05, *** p < 0.001, unpaired t test. (E) Incubation of IGF-1 for 24 – 48 h in cultured PC12 cells produced an increase in Cav3.2 protein compared to the PBS treatment group. Upper: representative Western blot bands; lower: statistical analysis of protein expression. n = 7. ** p < 0.01, *** p < 0.001, one-way ANOVA with Bonferroni’s post hoc test. (F) JB-1, an antagonist of IGF-1R, prevented the BCP-stimulated accumulation of Cav3.2 compared to NS treatment rats. *** p < 0.001, BCP + NS vs. Sham + NS; # p < 0.05, BCP + JB-1 vs. BCP + NS, unpaired t test. (G and H) Three consecutive days of intrathecal application of JB-1 attenuated mechanical allodynia (G) and thermal hyperalgesia (H) 14 days after BCP. n = 8. *** p < 0.001, BCP + NS vs. Sham + NS; # p < 0.05, ## p < 0.01, ### p < 0.001, BCP + JB-1 vs. BCP + NS, two-way ANOVA with Bonferroni’s post hoc test.
Article Snippet: Based on a standard protocol, free-floating sections were washed in PBS, blocked in 10% normal goat serum with 0.3% Triton X-100 in PBS for 1 h at room temperature, and incubated with one of the following primary antibodies: rabbit anti-Cav3.2 antibody (1: 200, ACC-025, Alomone Labs), mouse anti-IGF-1R β antibody (1:50, sc-390130, Santa Cruz Biotechnology), mouse anti-ionized calcium binding adaptor 1 (IBA1, a microglia marker, 1: 200, ab283319, Abcam), mouse anti-glial fibrillary acidic protein (GFAP, an astrocyte marker, 1: 200, ab4648, Abcam) or mouse anti-neuronal specific nuclear protein (NeuN, a neuronal marker, 1: 200, 66836-1-Ig, Proteintech) in 1% bovine serum albumin (BSA) with 0.3% Triton X-100 at 4 °C for 24 h. Sections were then washed in PBS and incubated with one of the following secondary antibodies at room temperature for 2 h: Alexa Fluor 488 conjugated goat anti-rabbit IgG (1: 100, 111-545-003, Jackson ImmunoResearch Laboratories), Alexa Fluor 568 conjugated goat anti-mouse IgG (1: 200, A-11004, Thermo Fisher Scientific), rinsed in PBS, then dried and covered with anti-fade mounting medium.
Techniques: Expressing, Inhibition, Western Blot, Incubation, Cell Culture, Produced