title: Role of the extracellular signal-regulated kinase 1/2 signaling pathway in the process of thrombin-promoting airway remodeling in ovalbumin-allergic rats.
abstract: BACKGROUND
  Although it is recognized that thrombin plays a key role in airway remodeling during chronic asthma. In a previous study, we have proved that thrombin promotes airway remodeling via PAR-1 in OVA-allergic rats, but little is known about intracellular signaling pathway involved in the event.
  
  
  OBJECTIVE
  In this study, we intend to explore the impact of pERK1/2 signaling pathway on the process of thrombin-induced airway remodeling in OVA-allergic rats.
  
  
  METHODS
  A rat model of chronic asthma was set up by systemic sensitization and repeated challenge to OVA. The doses of thrombin, recombinant hirudin, PAR-1 inhibitor ER-112780-06, and pERK1/2 inhibitor PD98059 varied for different groups. The expression of pERK1/2 was analyzed by western blot and RT-PCR. Secretion of TGF-β1 and IL-6 was detected by ELISA.
  
  
  RESULTS
  The expression of pERK1/2 was higher in the airway of asthmatic rats than those of normal rats, and was significantly increased by thrombin treatment but decreased by thrombin-inhibitor treatment. Airway remodeling was enhanced by thrombin but weakened by pERK1/2 inhibitor. Expression of growth factors and IL-6 in asthmatic rats was significantly increased by thrombin treatment and decreased by thrombin-inhibitor treatment and pERK1/2 inhibitor treatment.
  
  
  CONCLUSIONS
  These results suggest that ERK1/2 signaling pathway may play an important role in the process of thrombin-promoting airway remodeling in OVA-allergic rats, and pERK1/2 inhibitor effectively inhibits the process.
authors.affiliation: Department of Pediatrics .
authors.forename: Meirong
authors.initials: M
authors.lastname: Bi
authors.forename: Aili
authors.initials: A
authors.lastname: Guo
authors.forename: Hongyang
authors.initials: H
authors.lastname: Zhao
authors.forename: Xuewu
authors.initials: X
authors.lastname: Sun
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Guohong
authors.initials: G
authors.lastname: Shen
authors.forename: Xueying
authors.initials: X
authors.lastname: Wang
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Mi
authors.initials: M
authors.lastname: Xu
authors.forename: Mingming
authors.initials: M
authors.lastname: Qin
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhu
mesh_terms: D000280:Administration, Inhalation; D056151:Airway Remodeling / Q000187:drug effects / Q000276:immunology*; D000818:Animals; D000991:Antithrombins / Q000494:pharmacology; D001249:Asthma / Q000201:enzymology / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006629:Hirudins / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000276:immunology; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D017208:Rats, Wistar; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D010975:Platelet Aggregation Inhibitors
chemical_list: D000991:Antithrombins; D006629:Hirudins; D015850:Interleukin-6; D053773:Transforming Growth Factor beta1; D010047:Ovalbumin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D013917:Thrombin; D010975:Platelet Aggregation Inhibitors
keywords: Airway remodeling; PD98059; asthma; pERK1/2; rat; thrombin