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

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

doi:10.3389/fncel.2018.00437

Frontiers in Cellular Neuroscience (Nov 2018)

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

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

Affiliations

Dandan Tan: Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, China
Dandan Tan: Department of Histology and Embryology, Southern Medical University, Guangzhou, China
Jinkun Wen: Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, China
Jinkun Wen: Department of Histology and Embryology, Southern Medical University, Guangzhou, China
Lixia Li: Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, China
Lixia Li: Department of Histology and Embryology, Southern Medical University, Guangzhou, China
Xianghai Wang: Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, China
Xianghai Wang: Department of Histology and Embryology, Southern Medical University, Guangzhou, China
Changhui Qian: Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, China
Changhui Qian: Department of Histology and Embryology, Southern Medical University, Guangzhou, China
Changhui Qian: Department of Histology and Embryology, Fujian University of Traditional Chinese Medicine, Fuzhou, China
Mengjie Pan: Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, China
Mengjie Pan: Department of Histology and Embryology, Southern Medical University, Guangzhou, China
Muhua Lai: Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, China
Muhua Lai: Department of Histology and Embryology, Southern Medical University, Guangzhou, China
Junyao Deng: Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, China
Junyao Deng: Department of Histology and Embryology, Southern Medical University, Guangzhou, China
Xiaofang Hu: Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, China
Xiaofang Hu: Department of Histology and Embryology, Southern Medical University, Guangzhou, China
Haowen Zhang: Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, China
Haowen Zhang: Department of Histology and Embryology, Southern Medical University, Guangzhou, China
Jiasong Guo: Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, China
Jiasong Guo: Department of Histology and Embryology, Southern Medical University, Guangzhou, China
Jiasong Guo: Key Laboratory of Mental Health of the Ministry of Education, Southern Medical University, Guangzhou, China

DOI: https://doi.org/10.3389/fncel.2018.00437
Journal volume & issue: Vol. 12

Abstract

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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.

Published in Frontiers in Cellular Neuroscience

ISSN: 1662-5102 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: http://www.frontiersin.org/cellular-neuroscience

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