DAPK and CIP2A are involved in GAS6/AXL-mediated Schwann cell proliferation in a rat model of bilateral cavernous nerve injury
PDF | HTML | How to cite
Metrics: PDF 1838 views | HTML 1893 views | ?
Yen-Lin Chen1,2,3, Yi-Ting Tsai1, Ting-Ting Chao4, Yi-No Wu5, Meng-Chuan Chen6, Ying-Hung Lin3, Chun-Hou Liao3,7, Shang-Shing P. Chou2 and Han-Sun Chiang3,7
1Department of Pathology, Cardinal Tien Hospital, New Taipei, Taiwan
2Department of Chemistry, Fu-Jen Catholic University, New Taipei, Taiwan
3Graduate Institute of Biomedical and Pharmaceutical Science, Fu-Jen Catholic University, New Taipei, Taiwan
4Medical Research Center, Cardinal Tien Hospital, New Taipei, Taiwan
5School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan
6Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
7Division of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei, Taiwan
Han-Sun Chiang, email: [email protected]
Keywords: cavernous nerve; Schwann cell; CIP2A; DAPK; GAS6/AXL
Received: July 22, 2017 Accepted: October 28, 2017 Published: January 05, 2018
Purpose: Impotence is one of the major complications occurring in prostate cancer patients after radical prostectomy (RP). Self-repair of the injured nerve has been observed in animal models and in patients after RP. However, the downstream signalling is not well documented. Here, we found that the DAPK/CIP2A complex is involved in GAS6/AXL-related Schwann cell proliferation.
Materials and Methods: The 3 groups were a sham group, a 14-day post-bilateral cavernous nerve injury (BCNI) group and a 28-day post-BCNI group. Erectile function was assessed and immunohistochemistry was performed. The rat Schwann cell RSC96 line was chosen for gene knockdown, cell viability, western blot, immunofluorescence and co-immunoprecipitation assays.
Results: The intracavernosal pressure was low on the 14th day after BCNI and partially increased by the 28th day. GAS6 and p-AXL expression gradually increased in the cavernous nerve after BCNI. RSC96 cells incubated with a GAS6 ligand showed increased levels of p-ERK1/2 and p-AKT. Moreover, DAPK and CIP2A.p-AXL and p-DAPK and CIP2A complexes were identified by both immunoblotting and co-immunoprecipitation.
Conclusion: The DAPK/CIP2A complex is involved in GAS6/AXL-related Schwann cell proliferation. CIP2A inhibits PP2A activity, which results in p-DAPK(S308) maintenance and promotes Schwann cell proliferation. CIP2A is a potential target for the treatment of nerve injury after RP.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.