title: Inhibition of CXCL12/CXCR4 suppresses pulmonary arterial smooth muscle cell proliferation and cell cycle progression via PI3K/Akt pathway under hypoxia.
abstract: Stromal cell-derived factor 1 (CXCL12) and its receptor CXC chemokine receptor 4 (CXCR4) are known to modulate hypoxia-induced pulmonary hypertension (PH) and vascular remodeling by mobilization and recruitment of progenitor cells to the pulmonary vasculature. However, little is known about CXCL12/CXCR4 regulating proliferation and cell cycle progression of pulmonary arterial smooth muscle cells (PASMCs). To determine whether CXCL12/CXCR4 regulates PASMC proliferation and the cell cycle, immunohistochemistry, Western blot, bromodeoxyuridine incorporation and cell cycle analysis were preformed in this study. Our results showed that CXCR4 was induced by hypoxia in pulmonary arteries and PASMCs of rats. Hypoxia-increased cell viability, DNA synthesis and proliferating cell nuclear antigen expression were blocked by administration of CXCR4 antagonist AMD3100, silencing CXCR4 or CXCL12. Furthermore, inhibition of CXCL12/CXCR4 suppressed cell cycle progression, decreased the number of cells in S+G2/M phase and attenuated the expression of proteins that regulate the cell cycle progression at these phases. In addition, PI3K/Akt signaling mediated CXCL12/CXCR4 regulating proliferation and cell cycle progression in PASMCs. Thus, these results indicate that blockade of CXCL12/CXCR4 inhibited PASMC proliferation and cell cycle progression in hypoxia-induced PH via PI3K/Akt signaling pathway.
authors.affiliation: a Department of Biopharmaceutical Sciences , College of Pharmacy, Harbin Medical University-Daqing , Daqing , China and.
authors.forename: Liuping
authors.initials: L
authors.lastname: Wei
authors.affiliation: a Department of Biopharmaceutical Sciences , College of Pharmacy, Harbin Medical University-Daqing , Daqing , China and.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: a Department of Biopharmaceutical Sciences , College of Pharmacy, Harbin Medical University-Daqing , Daqing , China and.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Cao
authors.affiliation: a Department of Biopharmaceutical Sciences , College of Pharmacy, Harbin Medical University-Daqing , Daqing , China and.
authors.forename: Hao
authors.initials: H
authors.lastname: Xing
authors.affiliation: a Department of Biopharmaceutical Sciences , College of Pharmacy, Harbin Medical University-Daqing , Daqing , China and.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Yu
authors.affiliation: a Department of Biopharmaceutical Sciences , College of Pharmacy, Harbin Medical University-Daqing , Daqing , China and.|b Biopharmaceutical Key Laboratory of Heilongjiang Province , Harbin , China.
authors.forename: Daling
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000473:pathology / Q000503:physiopathology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D066253:Vascular Remodeling / Q000502:physiology
chemical_list: C575935:CXCL12 protein, rat; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: CXCL12; CXCR4; Cell cycle; proliferation; pulmonary arterial smooth muscle cell