Glycoprotein non-metastatic melanoma B interacts with epidermal growth factor receptor to regulate neural stem cell survival and differentiation

The functional recovery following spinal cord injury (SCI) remains a challenge clinically. Among the proteins interacted with the glycoprotein non-metastatic melanoma B (GPNMB), epidermal growth factor receptor (EGFR) during activation is able to promote the proliferation of neural stem cells (NSCs) in the spinal cord. We investigated the roles of GPNMB and EGFR in regulating the survival and differentiation of the NSCs. By overexpression and short-hairpin RNA-mediated knockdown of GPNMB in the NSCs, GPNMB promoted cell viability and differentiation by increasing the expressions of βIII tubulin and CNPase (2′,3′-cyclic nucleotide 3-phosphodiesterase). Using co-immunoprecipitation, we found that EGFR interacted with GPNMB. Furthermore, EGFR had a similar effect as GPNMB on promoting cell viability and differentiation. Overexpression of EGFR reversed the decrease in viability and differentiation caused by the knockdown of GPNMB, and vice versa. Last but not least, we tested the effect of GPNMB and EGFR on several intracellular pathways and found that GPNMB/EGFR modulated the phosphorylated (p)-c-Jun N-terminal kinase (JNK)1/2/JNK1/2 ratio and the p-nuclear factor κB (NF-κB p65)/NF-κB p65 ratio. In sum, our findings demonstrate the interaction between GPNMB and EGFR that regulates cell bioprocesses, with the hope to provide a new strategy of SCI therapy.