c-Jun/AP-1 transcription factor regulates laminin-1-induced neurite outgrowth in human bone marrow mesenchymal stem cells: role of multiple signaling pathways.

In this study, we demonstrated that laminin-1 (LM-1) induces neurite outgrowth and enhances the expression of neurofilament-L and MAP2 in human bone marrow mesenchymal stem cells (MSCs). The c-Jun transcription factor was strongly activated by LM-1 during neurite induction. Suppression of c-Jun inhibited the expression of the c-Jun target genes α6 integrin and neurofilament-L, resulting in the loss of neurite outgrowth. Additionally, we found that the LM-1-α6 integrin interaction stimulated phosphorylation of FAK, leading to the activation of JNK and Akt. Pharmacological inhibition of these pathways blocked c-Jun activation and neurite outgrowth. Collectively, our findings suggest that c-Jun/AP-1 activity mediated by JNK, PI3K/Akt and ERK pathways is required for LM-1-induced neurite outgrowth in human bone marrow MSCs.