High glucose promotes vascular smooth muscle cell proliferation by upregulating proto-oncogene serine/threonine-protein kinase Pim-1 expression
| Autor: | Xiaojiang Deng, Keke Wang, Rujia Li, Wei Jie, Zhihua Shen, Junli Guo, Xiaomin Liao, Ranran Ding, Yanping Ha, Yue-Qiong Kong, Yuyou Wu, Yanan Jia, Sisi Wang |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Neointima Vascular smooth muscle Cell Serine threonine protein kinase 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases Pathology Section medicine Oncogene biology Cell growth Kinase business.industry Pim-1 Research Paper: Pathology high glucose Proliferating cell nuclear antigen STAT3 signaling cell proliferation 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Immunology Cancer research biology.protein vascular smooth muscle cell business |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Keke Wang 1,* , Xiaojiang Deng 2,* , Zhihua Shen 1 , Yanan Jia 1 , Ranran Ding 3 , Rujia Li 1 , Xiaomin Liao 1 , Sisi Wang 1 , Yanping Ha 1 , Yueqiong Kong 4 , Yuyou Wu 4 , Junli Guo 4 and Wei Jie 1 1 Department of Pathology, School of Basic medicine Sciences, Guangdong Medical University, Zhanjiang, P.R. China 2 Department of Cardiovascular, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China 3 Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China 4 Cardiovascular Institute of 1st Affiliated Hospital & Key Laboratory of Tropical Diseases and Translational Medicine of Ministry of Education, Hainan Medical University, Haikou, P.R. China * Joint first authors Correspondence to: Junli Guo, email: // Wei Jie, email: // Keywords : high glucose, vascular smooth muscle cell, Pim-1, cell proliferation, STAT3 signaling, Pathology Section Received : March 09, 2017 Accepted : June 28, 2017 Published : July 18, 2017 Abstract Serine/threonine kinase proviral integration site for Moloney murine leukemia virus 1 (Pim-1) plays an essential role in arterial wall cell proliferation and associated vascular diseases, including pulmonary arterial hypertension and aortic wall neointima formation. Here we tested a role of Pim-1 in high-glucose (HG)-mediated vascular smooth muscle cell (VSMC) proliferation. Pim-1 and proliferating cell nuclear antigen (PCNA) expression levels in arterial samples from streptozotocin-induced hyperglycemia rats were increased, compared with their weak expression in normoglycemic groups. In cultured rat VSMCs, HG led to transient Pim-1 expression decline, followed by sustained expression increase at both transcriptional and translational levels. Immunoblot analysis demonstrated that HG increased the expression of the 33-kDa isoform of Pim-1, but at much less extent to its 44-kDa plasma membrane isoform. D-glucose at a concentration of 25 mmol/L showed highest activity in stimulating Pim-1 expression. Both Pim-1 inhibitor quercetagetin and STAT3 inhibitor stattic significantly attenuated HG-induced VSMC proliferation and arrested cell cycle progression at the G1 phase. Quercetagetin showed no effect on Pim-1 expression but decreased the phosphorylated-Bad (T112)/Bad ratio in HG-treated VSMCs. However, stattic decreased phosphorylated-STAT3 (Y705) levels and caused transcriptional and translational down-regulation of Pim-1 in HG-treated VSMCs. Our findings suggest HG-mediated Pim-1 expression contributes to VSMC proliferation, which may be partly due to the activation of STAT3/Pim-1 signaling. |
| Databáze: | OpenAIRE |
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