Inhibition of RhoA-Subfamily GTPases Suppresses Schwann Cell Proliferation Through Regulating AKT Pathway Rather Than ROCK Pathway

Dandan Tan; Jinkun Wen; Lixia Li; Xianghai Wang; Changhui Qian; Mengjie Pan; Muhua Lai; Junyao Deng; Xiaofang Hu; Haowen Zhang; Jiasong Guo

doi:10.3389/fncel.2018.00437

Inhibition of RhoA-Subfamily GTPases Suppresses Schwann Cell Proliferation Through Regulating AKT Pathway Rather Than ROCK Pathway

Front Cell Neurosci. 2018 Nov 20:12:437. doi: 10.3389/fncel.2018.00437. eCollection 2018.

Authors

Dandan Tan^{1

2}, Jinkun Wen^{1

2}, Lixia Li^{1

2}, Xianghai Wang^{1

2}, Changhui Qian^{1

2

3}, Mengjie Pan^{1

2}, Muhua Lai^{1

2}, Junyao Deng^{1

2}, Xiaofang Hu^{1

2}, Haowen Zhang^{1

2}, Jiasong Guo^{1

2

4}

Affiliations

¹ Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, China.
² Department of Histology and Embryology, Southern Medical University, Guangzhou, China.
³ Department of Histology and Embryology, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
⁴ Key Laboratory of Mental Health of the Ministry of Education, Southern Medical University, Guangzhou, China.

Abstract

Inhibiting RhoA-subfamily GTPases by C3 transferase is widely recognized as a prospective strategy to enhance axonal regeneration. When C3 transferase is administered for treating the injured peripheral nerves, Schwann cells (SCs, important glial cells in peripheral nerve) are inevitably impacted and therefore SC bioeffects on nerve regeneration might be influenced. However, the potential role of C3 transferase on SCs remains elusive. Assessed by cell counting, EdU and water-soluble tetrazolium salt-1 (WST-1) assays as well as western blotting with PCNA antibody, herein we first found that CT04 (a cell permeable C3 transferase) treatment could significantly suppress SC proliferation. Unexpectedly, using Y27632 to inhibit ROCK (the well-accepted downstream signal molecule of RhoA subfamily) did not impact SC proliferation. Further studies indicated that CT04 could inactivate AKT pathway by altering the expression levels of phosphorylated AKT (p-AKT), PI3K and PTEN, while activating AKT pathway by IGF-1 or SC79 could reverse the inhibitory effect of CT04 on SC proliferation. Based on present data, we concluded that inhibition of RhoA-subfamily GTPases could suppress SC proliferation, and this effect is independent of conventional ROCK pathway but involves inactivation of AKT pathway.

Keywords: AKT; C3 transferase; ROCK; RhoA-subfamily GTPase; Schwann cell; proliferation.