title: Activation of Notch3 promotes pulmonary arterial smooth muscle cells proliferation via Hes1/p27Kip1 signaling pathway.
abstract: Activation of the Notch3 cascade is involved in the development of pulmonary arterial hypertension by stimulating the proliferation of vascular smooth muscle cells. However, the detailed molecular mechanisms underlying this effect are still unclear. The present study aims to address this issue. We demonstrated that over-expression of intracellular domain of the Notch3 receptor (NICD3) by adenovirus transfection dramatically induced proliferation of primary cultured pulmonary artery smooth muscle cells. This was accompanied with up-regulation of Hes1 protein and down-regulation of p27Kip1 protein. More importantly, we observed that prior silencing of Hes1 with siRNA blocked NICD3 over-expression-induced p27Kip1 reduction and cell proliferation. The present study suggests that Hes1 lies downstream of NICD3 and particularly mediates Notch3 signaling-induced proliferation of pulmonary arterial smooth muscle cells by down-regulation of p27Kip1 expression.
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Xi'an Children's Hospital, Xi'an, Shaanxi 710003, PR China.
authors.forename: Haoxiang
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Yanting
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Lan
authors.initials: L
authors.lastname: Yang
authors.affiliation: Departments of Anesthesiology, Physiology, and Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Manxiang
authors.initials: M
authors.lastname: Li
keywords: Hes1; NICD3; P27Kip1; PAH, pulmonary arterial hypertension; PAP, pulmonary arterial pressure; PASMCs; PASMCs, pulmonary arterial smooth muscle cells; Proliferation