title: Platelet-derived growth factor-B (PDGF-B) induced by hypoxia promotes the survival of pulmonary arterial endothelial cells through the PI3K/Akt/Stat3 pathway.
abstract: OBJECTIVE
  Pulmonary arterial endothelial plexiform lesions are a basic pathological change associated with pulmonary vascular remodeling and are characterized by the formation of tumorlets as a result of over-growth of endothelial cells. Accumulating evidence suggests that platelet-derived growth factor (PDGF) participates in regulating the progression of pulmonary arterial hypertension. However, whether PDGF promotes the survival of pulmonary arterial endothelial cells (PAECs), as well as the specific molecular mechanisms that underlie its actions, remains unknown.
  
  
  METHODS
  MTT assays, caspase-3 and caspase-9 activity assays and western blot analysis were performed.
  
  
  RESULTS
  We found that both the mRNA and protein expression of PDGF-B was induced by hypoxia and that the inhibitory effects exerted by hypoxia on apoptosis were attenuated by inhibitors of PDGF beta. Moreover, PDGF-B inhibited apoptosis in a dose-dependent manner by stimulating the phosphorylation of both Akt and Stat3, and the PI3K/AKT pathway serves as an up-stream participant in the Stat3 activation stimulated by PDGF-B. Additionally, the anti-apoptotic effects of PDGF-B were abolished when PAECs were treated with either an inhibitor or small interfering RNA targeting Stat3.
  
  
  CONCLUSIONS
  These observations suggest that PDGF-B is induced by hypoxia and protects against apoptosis via the PI3K/Akt/Stat3 signaling pathway.
authors.affiliation: Department of Hematology, the First Affiliated Clinical Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Limin
authors.initials: L
authors.lastname: Li
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Xu
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
authors.forename: Chengfang
authors.initials: C
authors.lastname: Lv
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Zhang
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Yu
authors.forename: Mingwen
authors.initials: M
authors.lastname: Zhang
authors.forename: Yueyue
authors.initials: Y
authors.lastname: Fu
authors.forename: Hongbin
authors.initials: H
authors.lastname: Meng
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis; D001549:Benzamides / Q000494:pharmacology; D002417:Cattle; D015687:Cell Hypoxia; D002470:Cell Survival; D002867:Chromones / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D000068877:Imatinib Mesylate; D020935:MAP Kinase Signaling System; D009025:Morpholines / Q000494:pharmacology; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics* / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology* / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D001549:Benzamides; D002867:Chromones; D009025:Morpholines; D010879:Piperazines; D020574:Proto-Oncogene Proteins c-sis; D011743:Pyrimidines; D020032:Tyrphostins; C106250:6,7-dimethoxy-3-phenylquinoxaline; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D000068877:Imatinib Mesylate