Tissue kallikrein mediates neurite outgrowth through epidermal growth factor receptor and flotillin-2 pathway in vitro |
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| Institution: | 1. Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, No.12 Mid. Wulumuqi Road, Shanghai 200040, PR China;2. Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No.110 Ganhe Road, Shanghai 200437, PR China;3. Department of Cardiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No.110 Ganhe Road, Shanghai 200437, PR China;1. Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austrian Workers'' Compensation Board (AUVA) Research Center, Vienna, Austria;2. Austrian Cluster for Tissue Regeneration, Vienna, Austria;3. Bernhard Gottlieb University Clinic of Dentistry, Universitätsklinik für Zahn-, Mund- und Kieferheilkunde Ges.m.b.H, Vienna, Austria;4. Medical University of Vienna, Department of Trauma Surgery, Vienna, Austria;5. University of Applied Sciences Technikum Wien, Department of Biochemical Engineering, Vienna, Austria;6. Red Cross Blood Transfusion Service of Upper Austria, Linz, Austria |
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| Abstract: | Tissue kallikrein (TK) was previously shown to take most of its biological effects through bradykinin receptors. In this study, we assumed that TK mediated neurite outgrowth was independent of bradykinin receptors. To test the hypothesis, we investigated TK-induced neurite outgrowth and its signaling mechanisms in cultured primary neurons and human SH-SY5Y cells. We found that TK stimulation could increase the number of processes and mean process length of primary neurons, which were blocked by epidermal growth factor receptor (EGFR) inhibitor or down-regulation, small interfering RNA for flotillin-2 and extracellular signal-regulated kinase (ERK) 1/2 inhibitor. Moreover, TK-induced neurite outgrowth was associated with EGFR and ERK1/2 activation, which were inhibited by EGFR antagonist or RNA interference and flotillin-2 knockdown. Interestingly, inhibition of bradykinin receptors had no significant effects on EGFR and ERK1/2 phosphorylation. In the present research, our data also suggested that EGFR and flotillin-2 formed constitutive complex that translocated to around the nuclei in the TK stimulation. In sum, our findings provided evidence that TK could promote neurite outgrowth via EGFR, flotillin-2 and ERK1/2 signaling pathway in vitro. |
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