<div>Effects of IGFBP-2 on proliferation and differentiation in neural stem cell line C17.2</div>

Abstract

Objective: Insulin-like growth factor binding protein-2 (IGFBP-2), a member of a highly conserved family of six insulin-like growth factor binding proteins (IGFBPs), can regulate several cellular processes through IGF-dependent or IGF-independent pathway. Recent studies have provided solid evidence for the importance to delineate that olfactory ensheathing cells (OEC)-conditioned medium (OCM) can not only facilitate the differentiation of neural stem cell line (C17.2) into neurons, but also promote the survival and proliferation. We have previously reported that IGFBP-2 was detected in OCM. This study is designed to investigate the roles of IGFBP-2 for the regulation of C17.2 differentiation and proliferation. Methods and results: IGFBP-2 was identified and upregulated in OCM to compare with astrocytes-conditioned medium by shotgun proteomics and semiquantitative proteomic analysis. In order to investigate whether exogenous IGFBP-2 could stimulate proliferation in C17.2 cells and differentiate it into glia or neuron, we used various concentrations of IGFBP-2 to induce C17.2 cells which were cultured in DMEM/F12. The results showed that exogenous IGFBP-2 can promote proliferation in C17.2 cells, but had little effect on differentiation. Interestingly, we also found that IGFBP-2 could induce C17.2 cells to differentiate into astrocytes, while inhibiting their differentiation into neurons in a dose-dependent manner when cultured C17.2 cells in OCM. Changes in cell morphology were imaged under a light microscope, and proliferating cells were counted. Cell viability was determined by MTT. In addition, Western blot, immunofluorescence, and flow cytometry analysis were performed to detect protein expression patterns of proliferation-related antigen, proliferating cell nuclear antigen, neuroectodermal stem cell marker, neuron specific class III beta tubulin, and glial fibrillary acidic protein. Conclusion: Exogenous IGFBP-2 could stimulate proliferation in C17.2 cells, and promote the differentiation of C17.2 cells into astrocytes induced by OCM. Its mechanism is related to activation of the extracellular signal-regulated kinase 1/2 pathway.

Improvement of Impaired Motor Functions by Human Dental Exfoliated Deciduous Teeth Stem Cell-Derived Factors in a Rat Model of Parkinson’s Disease

“…Overall, TGF-β1 is believed to exhibit important anti-inflammatory and regenerative effects on brain damage [30,47,48]. For IGFBP-2, it has been reported to stimulate the proliferation and differentiation of neural stem cells [49]. Together, these factors may mediate the neuroprotective mechanisms predicted according to the results of ELISA and RNA-seq (Figure 6B,C).…”

Cloning, gene regulation, and neuronal proliferation functions of novel N‐terminal–truncated carboxypeptidase E/neurotrophic factor‐αl variants in embryonic mouse brain

“…The known functions of IGFBP2 is to keep IGF-1 from binding to its receptor, but it also modulates cellular processes, independent of IGF-1 binding, in several tissues and cancer cells (31)(32)(33). Recently, IGFBP2 has been shown to stimulate proliferation and differentiation of neural stem cells to astrocytes through activation of the ERK signaling (34). Thus 40-kDa (CPE/NFa-1)-DN may promote proliferation and differentiation of embryonic neuronal progenitors and stem cells through up-regulation of IGFBP2 expression during development.…”