机构：[1]Vascular Surgery Department of Xuanwu Hospital, Institute of Vascular Surgery, Capital Medical University, Beijing, China血管外科首都医科大学宣武医院[2]Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, 1150 West Medical Center Dri, Rm 5556, MSRB-2, Ann Arbor, MI 48109, USA
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-beta superfamily signaling pathway members, Smad3 and BMPR2, in VSMC proliferation. Smad3 plays an important role in the TGF-beta/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.
基金：
the National Institute of Health (CA132755 and CA130899 to X.Y.)
the University of Michigan Cancer Center and GI Peptide Research Center
the Era of Hope Scholar Award from the Department of Defense
第一作者机构：[1]Vascular Surgery Department of Xuanwu Hospital, Institute of Vascular Surgery, Capital Medical University, Beijing, China
共同第一作者：
通讯作者：
通讯机构：[2]Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, 1150 West Medical Center Dri, Rm 5556, MSRB-2, Ann Arbor, MI 48109, USA
推荐引用方式(GB/T 7714)：
Tao Luo,Shijun Cui,Chunjing Bian,et al.Crosstalk between TGF-beta/Smad3 and BMP/BMPR2 signaling pathways via miR-17-92 cluster in carotid artery restenosis[J].MOLECULAR AND CELLULAR BIOCHEMISTRY.2014,389(1-2):169-176.doi:10.1007/s11010-013-1938-6.
APA：
Tao Luo,Shijun Cui,Chunjing Bian&Xiaochun Yu.(2014).Crosstalk between TGF-beta/Smad3 and BMP/BMPR2 signaling pathways via miR-17-92 cluster in carotid artery restenosis.MOLECULAR AND CELLULAR BIOCHEMISTRY,389,(1-2)
MLA：
Tao Luo,et al."Crosstalk between TGF-beta/Smad3 and BMP/BMPR2 signaling pathways via miR-17-92 cluster in carotid artery restenosis".MOLECULAR AND CELLULAR BIOCHEMISTRY 389..1-2(2014):169-176
