title: Crosstalk between TGF-β/Smad3 and BMP/BMPR2 signaling pathways via miR-17-92 cluster in carotid artery restenosis.
abstract: 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.
authors.affiliation: Vascular Surgery Department of Xuanwu Hospital, Institute of Vascular Surgery, Capital Medical University, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Luo
authors.forename: Shijun
authors.initials: S
authors.lastname: Cui
authors.forename: Chunjing
authors.initials: C
authors.lastname: Bian
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Yu
mesh_terms: D001483:Base Sequence; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics*; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D002339:Carotid Arteries / Q000378:metabolism*; D016893:Carotid Stenosis / Q000235:genetics*; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D062085:RNA, Long Noncoding; D015398:Signal Transduction / Q000235:genetics; D051900:Smad3 Protein / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D019485:Bone Morphogenetic Proteins; C568997:MIR17HG, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II