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Dynamic changes of Jab1 and p27kip1 expression in injured rat sciatic nerve
Xinghai Cheng1, Zhengming Zhou, Guangfei Xu
1Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, 226001, People's Republic of China.
Abstract:
Jun activation domain-binding protein (Jab1) is a multifunctional protein that participates in affecting signaling pathway, controlling cell proliferation and apoptosis, and regulating genomic instability and DNA repair, and acts as a key subunit of COP9 signalosome. p27kip1, a member of the Cip/Kip family of cyclin-dependent kinase inhibitors, was shown to inhibit the enzymatic activity of cyclin-CDK complexes, resulting in cell-cycle arrest at G1. Recent studies have shown that Jab1 directly binds to p27kip1 and induces nuclear export and subsequent degradation in a variety of human cancers, while the association and function of Jab1 and p27kip1 in nervous system lesion and regeneration remain unclear. Here, we performed a sciatic nerve injury model in adult rats and studied the dynamic changes of Jab1 and p27kip1 expression by Western blot. Sciatic nerve crush (SNC) resulted in a significant upregulation of Jab1 and a downregulation of p27kip1. Besides, we observed that Jab1 was expressed widely in Schwann cells (SCs) and had few co-localization in axons by double immunofluorescence staining. In addition, the peak expression of Jab1 was parallel with proliferating cell nuclear antigen (PCNA), and numerous SCs expressing Jab1 were PCNA-positive. Results obtained by co-immunoprecipitation and double labeling further showed their interaction in the sciatic nerve. Thus, these results suggested that Jab1 and p27kip1 may be involved in the pathophysiology of sciatic nerve after SNC.
Insights
Jun activation domain-binding protein (Jab1) and p27kip1 expression change after sciatic nerve crush injury in rats. Jab1 upregulation and p27kip1 downregulation suggest their involvement in nerve regeneration.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Jun activation domain-binding protein (Jab1) is a multifunctional protein involved in cell signaling, proliferation, apoptosis, and DNA repair.
- p27kip1 is a cyclin-dependent kinase inhibitor that regulates cell-cycle arrest.
- Jab1's interaction with p27kip1 in cancer is known, but its role in nervous system injury and regeneration is unclear.
Purpose of the Study:
- To investigate the dynamic changes and interaction of Jab1 and p27kip1 in a rat sciatic nerve injury model.
- To elucidate the potential roles of Jab1 and p27kip1 in the pathophysiology of sciatic nerve lesion and regeneration.
Main Methods:
- Adult rats underwent sciatic nerve crush (SNC) to create an injury model.
- Western blot was used to analyze dynamic changes in Jab1 and p27kip1 expression.
- Double immunofluorescence staining assessed Jab1 expression in Schwann cells and axons.
- Co-immunoprecipitation and double labeling confirmed the interaction between Jab1 and p27kip1.
Main Results:
- Sciatic nerve crush significantly upregulated Jab1 and downregulated p27kip1.
- Jab1 was predominantly expressed in Schwann cells and showed parallel expression with proliferating cell nuclear antigen (PCNA).
- Jab1 and p27kip1 were found to interact within the sciatic nerve.
Conclusions:
- Jab1 and p27kip1 expression is dynamically altered following sciatic nerve injury.
- The interaction and expression patterns suggest Jab1 and p27kip1 are involved in the cellular responses to sciatic nerve damage and potentially regeneration.
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