Molecular and Cellular Biochemistry

, Volume 389, Issue 1–2, pp 169–176 | Cite as

Crosstalk between TGF-β/Smad3 and BMP/BMPR2 signaling pathways via miR-17–92 cluster in carotid artery restenosis

  • Tao Luo
  • Shijun Cui
  • Chunjing Bian
  • Xiaochun Yu


In the recent decades, carotid angioplasty and stenting (CAS) has been developed into a credible option for the patients with carotid stenosis. However, restenosis remains a severe and unsolved issue after CAS treatment. Restenosis is characterized by neointimal hyperplasia, which is partially caused by vascular smooth muscle cells (VSMC) proliferation. However, the molecular mechanism involved in the restenosis is still unclear. In this study, we demonstrated a functional crosstalk between two TGF-β superfamily signaling pathway members, Smad3 and BMPR2, in VSMC proliferation. Smad3 plays an important role in the TGF-β/Smad3 signaling pathway, and is significantly upregulated in the carotid artery with restenosis to promote VSMC proliferation. In contrast, BMP receptor II (BMPR2), an inhibitor of VSMC proliferation is downregulated in carotid restenosis. We further found that BMPR2 downregulation is mediated by miR-17–92 cluster, which is transcriptionally regulated by Smad3. Thus, Smad3 upregulation and Smad3/miR-17–92 cluster-dependent BMPR2 downregulation are likely to promote VSMC proliferation and restenosis. Taken together, our results may provide novel clues for early diagnosis of carotid restenosis and developing new therapeutic strategy.


Carotid artery restenosis Smad3 BMPR2 miR-17–92 cluster 



This study was supported by the National Institute of Health (CA132755 and CA130899 to X.Y.), the University of Michigan Cancer Center and GI Peptide Research Center. X.Y. is a recipient of the Era of Hope Scholar Award from the Department of Defense.

Supplementary material

11010_2013_1938_MOESM1_ESM.xls (22 kb)
Supplementary material 1 (XLS 22 kb)


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Vascular Surgery Department of Xuanwu Hospital, Institute of Vascular SurgeryCapital Medical UniversityBeijingChina
  2. 2.Division of Molecular Medicine and Genetics, Department of Internal MedicineUniversity of Michigan Medical SchoolAnn ArborUSA

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