Abstract
The insulin-like growth factor (IGF) system is linked to CNS pathological states. The functions of IGFs are modulated by a family of binding proteins termed insulin-like growth factor binding proteins (IGFBPs). Here, we demonstrate that IGFBP-6 may be associated with neuronal apoptosis in the processes of intracerebral hemorrhage (ICH). We obtained a significant upregulation of IGFBP-6 in neurons adjacent to the hematoma following ICH with the results of Western blot, immunohistochemistry, and immunofluorescence. Increasing IGFBP-6 level was found to be accompanied by the upregulation of Bax, Bcl-2, and active caspase-3. Besides, IGFBP-6 co-localized well with active caspase-3 in neurons, indicating its potential role in neuronal apoptosis. Knocking down IGFBP-6 by RNA-interference in PC12 cells reduced active caspase-3 expression. Thus, IGFBP-6 may play a role in promoting the brain secondary damage following ICH.
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Authors’ Contributions
CD and LQ designed experiments; QD and PJ carried out experiments; YG, LZ, HD and ZY analyzed experimental results; HL analyzed sequencing data and developed analysis tools; XM wrote the manuscript.
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Qijun Dai and Peipei Jiang contributed equally to this work.
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10571_2016_453_MOESM1_ESM.tif
Fig. S1 Modulations of IGFBP-6 on cell apoptosis in vitro. Western blot showed siRNA-2 silenced IGFBP-6 in SH-SY5Y cells (A); the bar chart indicated the density of IGFBP-6 versus β-actin (B). The knockdown of IGFBP-6 induced decreasing levels of active caspase-3 and Bax and had up-regulation of Bcl-2 expression (C). The bar graph indicated the relative density of IGFBP-6, active caspase-3, Bax, and Bcl-2 versus β-actin (D). Data are presented as mean ± SEM. (n = 3, *, #, ^, & P < 0.05, significantly different from the control-siRNA-treated group). Immunofluorescent analysis of the colocalization between IGFBP-6 and active-caspase-3 in control, non-specific siRNA or IGFBP-6-siRNA-2 transfected SH-SY5Y cells after hemin treatment (E). Supplementary material 1 (TIFF 1704 kb)
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Dai, Q., Jiang, P., Gu, Y. et al. Insulin-like Growth Factor Binding Protein6 Associated with Neuronal Apoptosis Following Intracerebral Hemorrhage in Rats. Cell Mol Neurobiol 37, 1207–1216 (2017). https://doi.org/10.1007/s10571-016-0453-1
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DOI: https://doi.org/10.1007/s10571-016-0453-1