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Lentivirus‑mediated overexpression of CD97/ADGRE5 reverses dysregulated high glucose‑induced endothelial cell migration

  • Authors:
    • Wenting Zhao
    • Zhen Wang
    • Zewei Sun
    • Shuai Wang
    • Mingjie Wu
    • Liangrong Zheng
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
    Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3048-3054
    |
    Published online on: March 30, 2017
       https://doi.org/10.3892/mmr.2017.6417
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Abstract

Elevated blood glucose levels contribute to a series of complications in patients with diabetes mellitus, including chronic ulcers and accelerated atherosclerosis. Dysregulated endothelial migration induced by high glucose is important in vascular‑associated complications. In the present study, cluster of differentiation (CD)97/adhesion G protein‑coupled receptor 5 (ADGRE5), a member of the G protein‑coupled receptor protein family, stimulated angiogenesis was investigated to determine its role in cell models of diabetes mellitus using lentivirus‑mediated overexpression and siRNA transfection. The results revealed reduced expression in high glucose‑treated human umbilical vein endothelial cells and in the endothelium of diabetic mice. Among the three CD97 isoforms, the majority of the expression of CD97 (EGF1,2,5) in the endothelial cells was regulated by high levels of glucose. Using stable lentivirus‑mediated transfection and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‑associated protein 9 (Cas9) technology, the present study constructed CD97‑overexpression and CD97‑knockout endothelial cell lines. Migration assays showed that the lentivirus‑mediated overexpression of CD97/ADGRE5 improved the inhibition of high glucose‑induced endothelial cell migration. In addition, using cytoskeleton staining, it was found that CD97 promoted membrane ruffling and lamellipodia formation. Cell division cycle 42, a small GTP‑binding protein, and its downstream factor, actin‑related protein 2, were involved in CD97‑induced actin reorganization in endothelial cells. Additionally, the use of transcription factor filter plate assays revealed that the nuclear translocation of signal transducer and activator of transcription 1 stimulated by high glucose contributed to the inhibited transcription of CD97. In conclusion, the present study established that the overexpression of CD97 improved high glucose‑induced dysfunction of endothelial cell migration. These findings provide insight to assist in identifying therapeutic targets with potential to ameliorate certain vascular complications of diabetes.
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Copy and paste a formatted citation
Spandidos Publications style
Zhao W, Wang Z, Sun Z, Wang S, Wu M and Zheng L: Lentivirus‑mediated overexpression of CD97/ADGRE5 reverses dysregulated high glucose‑induced endothelial cell migration. Mol Med Rep 15: 3048-3054, 2017.
APA
Zhao, W., Wang, Z., Sun, Z., Wang, S., Wu, M., & Zheng, L. (2017). Lentivirus‑mediated overexpression of CD97/ADGRE5 reverses dysregulated high glucose‑induced endothelial cell migration. Molecular Medicine Reports, 15, 3048-3054. https://doi.org/10.3892/mmr.2017.6417
MLA
Zhao, W., Wang, Z., Sun, Z., Wang, S., Wu, M., Zheng, L."Lentivirus‑mediated overexpression of CD97/ADGRE5 reverses dysregulated high glucose‑induced endothelial cell migration". Molecular Medicine Reports 15.5 (2017): 3048-3054.
Chicago
Zhao, W., Wang, Z., Sun, Z., Wang, S., Wu, M., Zheng, L."Lentivirus‑mediated overexpression of CD97/ADGRE5 reverses dysregulated high glucose‑induced endothelial cell migration". Molecular Medicine Reports 15, no. 5 (2017): 3048-3054. https://doi.org/10.3892/mmr.2017.6417
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao W, Wang Z, Sun Z, Wang S, Wu M and Zheng L: Lentivirus‑mediated overexpression of CD97/ADGRE5 reverses dysregulated high glucose‑induced endothelial cell migration. Mol Med Rep 15: 3048-3054, 2017.
APA
Zhao, W., Wang, Z., Sun, Z., Wang, S., Wu, M., & Zheng, L. (2017). Lentivirus‑mediated overexpression of CD97/ADGRE5 reverses dysregulated high glucose‑induced endothelial cell migration. Molecular Medicine Reports, 15, 3048-3054. https://doi.org/10.3892/mmr.2017.6417
MLA
Zhao, W., Wang, Z., Sun, Z., Wang, S., Wu, M., Zheng, L."Lentivirus‑mediated overexpression of CD97/ADGRE5 reverses dysregulated high glucose‑induced endothelial cell migration". Molecular Medicine Reports 15.5 (2017): 3048-3054.
Chicago
Zhao, W., Wang, Z., Sun, Z., Wang, S., Wu, M., Zheng, L."Lentivirus‑mediated overexpression of CD97/ADGRE5 reverses dysregulated high glucose‑induced endothelial cell migration". Molecular Medicine Reports 15, no. 5 (2017): 3048-3054. https://doi.org/10.3892/mmr.2017.6417
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