Exendin-4 promotes actin cytoskeleton rearrangement and protects cells from Nogo-A-Δ20 mediated spreading inhibition and growth cone collapse by down-regulating RhoA expression and activation via the PI3K pathway

• Published in: Biomedicine & pharmacotherapy Vol. 109; pp. 135 - 143
• Main Authors: Zhao, Fei, Li, jianwei, Wang, Renjie, Xu, Huiyou, Ma, Ke, Kong, Xianbin, Sun, Zhonglei, Niu, Xuegang, Jiang, Jipeng, Liu, Baohu, Li, Bo, Duan, Feng, Chen, Xuyi
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.01.2019; Elsevier
• Subjects: Cell migration; Cell spreading; Exendin-4; Growth cone; Nogo-A-Δ20; RhoA; Growth cone; Nogo-A-Δ20; RhoA; Cell spreading; Cell migration; Exendin-4
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.10.008

•Exendin-4 increases phosphorylation of cofilin and promotes actin cytoskeleton rearrangement.•Exendin-4 protects SH-SY5Y and PC12 cells from Nogo-A-Δ20-mediated spreading inhibition.•Exendin-4 induces SH-SY5Y differentiation and reduces Nogo-A-Δ20-mediated growth cone collapse.•Exendin-4 significantly reduce SH-SY5Y cell migration.•Exendin-4 decreases the expression and activation of RhoA/Rock1 via PI3K signaling pathway. Exendin-4 is a protein of the GLP-1 family currently used to treat diabetes. Recently, a greater number of biological properties have been associated with the GLP-1 family. Our data shows that exendin-4 treatment significantly increases the cytoskeleton rearrangement, which leads to an increasingly differentiated phenotype and reduced cell migration. We also found that exendin-4 could prevent SH-SY5Y and PC12 cells from Nogo-A-Δ20 mediated spreading inhibition and neurite collapse. Western blot analysis indicated that exendin-4 treatment both reduced the expression and activation of RhoA via the PI3K signaling pathway. These data suggest that exendin-4 may protect nerve regeneration by preventing the inhibition of Nogo-A via down-regulating RhoA expression and activation.