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Updated: Jun 5, 2026
In Vivo Gene Transfer to Schwann Cells in the Rodent Sciatic Nerve by Electroporation
Published on: September 8, 2016
Expressions of forkhead class box O 3a on crushed rat sciatic nerves and differentiated primary Schwann cells
Qiuhong Wang1, Youhua Wang, Zhengming Zhou
1Department of Orthopaedics, Affiliated Jiangyin Hospital of Nantong University, Nantong, China.
Abstract:
Forkhead box-containing protein, class O 3 a (FOXO3a), an Akt downstream target, plays an important role in peripheral nervous system. FOXO3a shares the ability to be inhibited and translocated from the nucleus on phosphorylation by proteins such as Akt/PKB in the PI3K signaling pathway. To elucidate the expression and possible function of FOXO3a in lesion and repair, we performed an acute sciatic nerve crush model and studied differential expressions of FOXO3a. We observed that expressions of FOXO3a in Schwann cells (SCs) of the peripheral nervous system and cAMP-induced differentiation were dynamically regulated. Western blot analysis showed FOXO3a level significantly decreased post injury. Moreover, Immunofluorescence double labeling suggested the changes were striking especially in SCs. In vitro, Western blot analysis showed that the expression of FOXO3a was decreased in cAMP-induced differentiated primary SCs. The FOXO3a siRNA-transfected SCs treated by cAMP promote differentiation of SCs through the PI3K/Akt pathway. The results indicate that FOXO3a plays an important role during differentiation of SCs.
Insights
Forkhead box-containing protein, class O 3 a (FOXO3a) expression decreases after sciatic nerve injury. This protein plays a key role in Schwann cell differentiation during peripheral nerve repair.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Forkhead box-containing protein, class O 3 a (FOXO3a) is a crucial Akt downstream target involved in peripheral nervous system functions.
- FOXO3a activity is regulated by phosphorylation and translocation within the PI3K/Akt signaling pathway.
Purpose of the Study:
- To investigate the expression and function of FOXO3a in the context of peripheral nerve injury and repair.
- To elucidate the role of FOXO3a in Schwann cell differentiation.
Main Methods:
- An acute sciatic nerve crush model was utilized to study differential gene expression.
- Western blot analysis and immunofluorescence double labeling were performed on nerve tissues and primary Schwann cells.
- Small interfering RNA (siRNA) was used to knockdown FOXO3a expression in Schwann cells.
Main Results:
- FOXO3a expression significantly decreased in Schwann cells following sciatic nerve injury.
- cAMP-induced differentiation of primary Schwann cells led to decreased FOXO3a expression.
- Knockdown of FOXO3a in Schwann cells promoted differentiation, suggesting its inhibitory role in this process via the PI3K/Akt pathway.
Conclusions:
- FOXO3a expression is dynamically regulated in Schwann cells during peripheral nerve injury and repair.
- FOXO3a plays an inhibitory role in Schwann cell differentiation.
- Modulating FOXO3a levels may offer therapeutic potential for peripheral nerve regeneration.
