title: Gene expression profiling of common signal transduction pathways affected by rBMSCs/F92A-Cav1 in the lungs of rat with pulmonary arterial hypertension.
abstract: BACKGROUND
  Pulmonary arterial hypertension (PAH) is associated with sustained vasoconstriction, inflammation and suppressed apoptosis of smooth muscle cells. Our previous studies have found that rat bone marrow-derived mesenchymal stem cells (rBMSCs) transduced with a mutant caveolin-1(F92A-Cav1) could enhance endothelial nitric oxide synthase (eNOS) activity and improve pulmonary vascular remodeling, but the potential mechanism is not yet fully explored. The present study was to investigate the gene expression profile upon rBMSCs/F92A-Cav1delivered to PAH rat to evaluate the role of F92A-Cav1 in its regulation.
  
  
  METHODS
  PAH was induced with monocrotaline (MCT, 60mg/kg) prior to delivery of lentiviral vector transduced rBMSCs expressing Cav1 or F92A-Cav1. Gene expression profiling was performed using Rat Signal Transduction PathwayFinder array. The expression changes of 84 key genes representing 10 signal transduction pathways in rat following rBMSCs/F92A-Cav1 treatment was examined.
  
  
  RESULTS
  Screening with the Rat Signal Transduction PathwayFinder R2PCR Array system and subsequent western blot, immunohistochemistry or real time PCR analysis revealed that F92A-Cav1 modified rBMSCs can inhibit the inflammation factors (TNF-alpha, Icam1 and C/EBPdelta), pro-proliferation genes (c-Myc, Bcl2a1d, Notch1and Hey2), oxidative stress gene (Hmox1) and activate cell cycle arrested gene Cdkn1a, ameliorating inflammation and inhibiting cell proliferation in PAH rat.
  
  
  CONCLUSIONS
  rBMSCs/F92A-Cav1 inhibits inflammation and cell proliferation by regulating signaling pathways that related to inflammation, proliferation, cell cycle and oxidative stress.
authors.affiliation: Central laboratory, and key Laboratory of Oral and Maxillofacial-Head and Neck Medical Biology, Liaocheng People's Hospital, Liaocheng, Shandong, 252000, China; Liaocheng People's Hospital and Clinical School of Taishan Medical University, Liaocheng, Shandong, China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Chen
authors.affiliation: Central laboratory, and key Laboratory of Oral and Maxillofacial-Head and Neck Medical Biology, Liaocheng People's Hospital, Liaocheng, Shandong, 252000, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Yang
authors.affiliation: Central laboratory, and key Laboratory of Oral and Maxillofacial-Head and Neck Medical Biology, Liaocheng People's Hospital, Liaocheng, Shandong, 252000, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Xu
authors.affiliation: Liaocheng People's Hospital and Clinical School of Taishan Medical University, Liaocheng, Shandong, China; Department of Cardiology, Liaocheng People's Hospital and Affiliated Liaocheng People's Hospital of Shandong University, Liaocheng, Shandong, 252000, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Yue
authors.affiliation: Department of Cardiology, Liaocheng People's Hospital and Affiliated Liaocheng People's Hospital of Shandong University, Liaocheng, Shandong, 252000, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xia
authors.affiliation: School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia.
authors.forename: Pádraig Michael
authors.initials: PM
authors.lastname: Strappe
authors.affiliation: Department of Cardiology, Liaocheng People's Hospital and Affiliated Liaocheng People's Hospital of Shandong University, Liaocheng, Shandong, 252000, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Central laboratory, and key Laboratory of Oral and Maxillofacial-Head and Neck Medical Biology, Liaocheng People's Hospital, Liaocheng, Shandong, 252000, China.
authors.forename: Li
authors.initials: L
authors.lastname: Pan
authors.affiliation: Central laboratory, and key Laboratory of Oral and Maxillofacial-Head and Neck Medical Biology, Liaocheng People's Hospital, Liaocheng, Shandong, 252000, China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Tang
authors.affiliation: Central laboratory, and key Laboratory of Oral and Maxillofacial-Head and Neck Medical Biology, Liaocheng People's Hospital, Liaocheng, Shandong, 252000, China.
authors.forename: Shuangfeng
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Liaocheng People's Hospital and Affiliated Liaocheng People's Hospital of Shandong University, Liaocheng, Shandong, 252000, China; School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia. Electronic address: lwang@csu.edu.au.
authors.forename: Lexin
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D051743:CCAAT-Enhancer-Binding Protein-delta
keywords: Bone marrow derived mesenchymal stem cells; Caveolin-1; Endothelial nitric oxide synthase; Nitric oxide; Pulmonary arterial hypertension