机构：[1]State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.[2]Division for Globalization Initiative, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.[3]Division of Oral Physiology, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.[4]Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.[5]Graduate School of Life Sciences, Tohoku University, Sendai 980-8577, Japan.[6]Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
This study evaluated the mechanism of temperature-controlled repeated thermal stimulation (TRTS)-mediated neuronal differentiation. We assessed the effect of SP600125, a c-Jun N-terminal kinase (JNK) inhibitor, on neuronal differentiation of rat PC12-P1F1 cells, which can differentiate into neuron-like cells by exposure to TRTS or neurotrophic factors, including bone morphogenetic protein (BMP) 4. We evaluated neuritogenesis by incubating the cells under conditions of TRTS and/or SP600125. Cotreatment with SP600125 significantly enhanced TRTS-mediated neuritogenesis, whereas that with other selective mitogen-activated protein kinase (MAPK) inhibitors did not-e.g., extracellular signal-regulated kinase (ERK)1/2 inhibitor U0126, and p38 MAPK inhibitor SB203580. We tried to clarify the mechanism of SP600125 action by testing the effect of U0126 and the BMP receptor inhibitor LDN193189 on the SP600125-mediated enhancement of intracellular signaling. SP600125-enhanced TRTS-induced neuritogenesis was significantly inhibited by U0126 or LDN193189. Gene expression analysis revealed that TRTS significantly increased β3-Tubulin, MKK3, and Smad7 gene expressions. Additionally, Smad6 and Smad7 gene expressions were substantially attenuated through SP600125 co-treatment during TRTS. Therefore, SP600125 may partly enhance TRTS-induced neuritogenesis by attenuating the negative feedback loop of BMP signaling. Further investigation of the mechanisms underlying the effect of SP600125 during TRTS-mediated neuritogenesis may contribute to the future development of regenerative neuromedicine.
基金：
Japan Society for the Promotion of
Science (KAKENHI grant numbers 16K11643 and K21K099290) and by the Cooperative Research Project Program of Joint Usage/Research Center at the Institute of Development, Aging, and Cancer,
Tohoku University.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|2 区生物学
小类|2 区化学：综合3 区生化与分子生物学
最新[2023]版：
大类|2 区生物学
小类|3 区生化与分子生物学3 区化学：综合
第一作者：
第一作者机构：[1]State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.[2]Division for Globalization Initiative, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
通讯作者：
推荐引用方式(GB/T 7714)：
Luo You-Ran,Kudo Tada-Aki,Tominami Kanako,et al.SP600125 Enhances Temperature-Controlled Repeated Thermal Stimulation-Induced Neurite Outgrowth in PC12-P1F1 Cells[J].International journal of molecular sciences.2022,23(24):doi:10.3390/ijms232415602.
APA：
Luo You-Ran,Kudo Tada-Aki,Tominami Kanako,Izumi Satoshi,Tanaka Takakuni...&Wang Hang.(2022).SP600125 Enhances Temperature-Controlled Repeated Thermal Stimulation-Induced Neurite Outgrowth in PC12-P1F1 Cells.International journal of molecular sciences,23,(24)
MLA：
Luo You-Ran,et al."SP600125 Enhances Temperature-Controlled Repeated Thermal Stimulation-Induced Neurite Outgrowth in PC12-P1F1 Cells".International journal of molecular sciences 23..24(2022)
生物学