title: Tanshinone IIA promotes pulmonary artery smooth muscle cell apoptosis in vitro by inhibiting the JAK2/STAT3 signaling pathway.
abstract: BACKGROUND
  Tanshinone IIA inhibits the proliferation of pulmonary artery smooth muscle cells (PASMCs), but the potential mechanisms of its effects on PASMCs apoptosis remain unclear.
  
  
  METHODS
  Rat were subjected to hypoxia for 9 days with or without Tanshinone IIA treatment. PASMCs were exposed to the conditions of 2% O2 and 93% N2 for 24 h in vitro. Hematoxylin and eosin (HE) staining was used to evaluate vascular remodeling. The Cell viability was determined using cell fluorescence staining and MTT assays, and apoptosis was assessed using flow cytometry. Protein expression was quantified by Western blotting.
  
  
  RESULTS
  Our results showed that Tanshinone IIA treatment reduced pulmonary artery media thickening in hypoxic rats. Tanshinone IIA reduced PASMC viability in a dose-dependent manner. Additionally, Tanshinone IIA promoted PASMC apoptosis, lowered Hsp60 levels, and upregulated caspase-3 expressions under hypoxic conditions. This pro-apoptotic effect of Tanshinone IIA might be due to the reduction of the phosphorylation of JAK2/STAT3 signaling markers and the increase in the levels of the downstream target, Cx43 in PASMCs.
  
  
  CONCLUSIONS
  These data suggest that Tanshinone IIA promotes PASMC apoptosis during hypoxia and reverses vascular remodeling. This effect is mediated by modulating the expression of Hsp60, caspase-3, and Cx43 via the JAK2/STAT3 signaling pathway. These results might provide a new therapeutic target to explore a novel strategy for hypoxia-induced vessel remodeling.
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Daqing, China.
authors.forename: Minggang
authors.initials: M
authors.lastname: Chen
authors.forename: Yumei
authors.initials: Y
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Yi
authors.forename: Liuping
authors.initials: L
authors.lastname: Wei
authors.forename: Yumei
authors.initials: Y
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000378:metabolism; D018031:Connexin 43 / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011651:Pulmonary Artery / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects; D066253:Vascular Remodeling / Q000187:drug effects
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D018834:Chaperonin 60; D018031:Connexin 43; D050796:STAT3 Transcription Factor; C021751:tanshinone; D053614:Janus Kinase 2; D053148:Caspase 3