Chinese Journal of Tissue Engineering Research ›› 2011, Vol. 15 ›› Issue (37): 6942-6946.doi: 10.3969/j.issn.1673-8225.2011.37.024

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Overexpression of cellular repressor of E1A-stimulated genes inhibits migration of vascular smooth muscle cells

Yan Cheng-hui, Luan Bo, Li Jie, Zhang Xiao-lin, Han Ya-ling   

  1. Department of Cardiology, Research Institute of Cardiovascular Diseases, General Hospital of Shenyang Military Area Command of Chinese PLA, Shenyang  110840, Liaoning Province, China
  • Received:2011-04-05 Revised:2011-07-18 Online:2011-09-10 Published:2011-09-10
  • Contact: Han Ya-ling, M.D., Professor, Doctoral supervisor. Department of Cardiology, Research Institute of Cardiovascular Diseases, General Hospital of Shenyang Military Area Command of Chinese PLA, Shenyang 110840, Liaoning Province, China hanyaling@263.net
  • About author:Yan Cheng-hui☆, Doctor, Associate chief technician, Department of Cardiology, Research Institute of Cardiovascular Diseases, General Hospital of Shenyang Military Area Command of Chinese PLA, Shenyang 110840, Liaoning Province, China yanch1029@ 163.com
  • Supported by:

    the National Natural Science Foundation of China (General Program), No. 30770793*, 30971218*, 81070097*; Youth Foundation Program of the National Natural Science Foundation of China, No. 30800465*; the Natural Science Foundation of Liaoning Province, No. 20092088*; High-Tech Research and Development Program of Liaoning Province, No. 2009225009-9*

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Abstract:

BACKGROUND: Loss of homeostasis in mature vascular smooth muscle cells (VSMCs) plays an important role in senescence of blood vessel. However, the molecular mechanism remains unknown.
OBJECTIVE: To investigate the molecular mechanism by which cellular repressor of E1A-stimulated genes (CREG) inhibits the migration of VSMCs.
METHODS: The pRc/CMV-CREG plasmid or the pSM2-siCREG plasmid was transferred into human VSMCs to produce the cell clone that overexpresses or downregulates CREG respectively. Cell scrape assay and Transwell assay were used to detect the migration of VSMCs. The CREG protein expression, matrix metalloproteinases (MMPs) and JNK expression and activation in cells before and after transfection were detected by western blot analysis. The effect of above-mentioned signal molecule expression on VSMCs migration was analyzed through the use of JNK and MMP9 inhibitor.
RESULTS AND CONCLUSION: Western blot analysis identified that CREG protein expression in hVSMCs-CREG cells increased (P < 0.05), but it was significantly decreased in the hVSMCs-siCREG cells (P < 0.05), compared with control ones. Cell scrape assay and Transwell assay results showed the migration of VSMCs was obviously inhibited in the hVSMCs-CREG group than in the normal control group. However, the migration of VSMCs in the hVSMCs-siCREG group was significantly increased  (P < 0.05). Western blot analysis and gelatinase spectrum analysis showed that MMP9 activity in the hVSMCs-siCREG group was significantly increased (P < 0.05) and at the same time, JNK protein was activated. Blocking study using JNK inhibitor confirmed that CREG promoted VSMCs migration by regulating JNK and MMP9. Results showed that CREG protein expression can inhibit the migration of VSMCs cultured in vitro by inhibiting the activation of JNK and MMP9.

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