Thrombin promotes airway remodeling via protease-activated receptor-1 and transforming growth factor-β1 in ovalbumin-allergic rats.
BACKGROUND
Protease-activated receptor-1 (PAR-1) is widely distributed in platelets and involved in coagulation cascade activated by thrombin. In this study, we intend to explore the role of PAR-1 in the process of thrombin-inducing transforming growth factor-β1 (TGF-β1) to promote airway remodeling in ovalbumin (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 varied for different groups. We evaluated the bronchoalveolar lavage fluid (BALF) concentration of thrombin in these groups. The protein and gene expression of PAR-1 was assessed and the expression of TGF-β1 was also detected.


RESULTS
The PAR-1 mRNA level and the protein level were higher in the airway of asthmatic rats than those of normal rats, and were significantly increased by thrombin treatment but decreased by thrombin-inhibitor treatment. Airway remodeling was strengthened by thrombin but weakened by thrombin inhibitor and PAR-1 antagonist. Expression of TGF-β1 protein in asthmatic rats was significantly increased by thrombin treatment and decreased by thrombin-inhibitor treatment and PAR-1 antagonist treatment.


CONCLUSIONS
The expression of PAR-1 is regulated by thrombin that induces the expression of TGF-β1 to promote airway remodeling via PAR-1 in OVA-allergic rats.
Department of Pediatrics, Jinan Central Hospital Affiliated to Shandong Univeristy, Jinan, China. keyanzxyy@163.com
Weiwei
W
Zhu
Meirong
M
Bi
Yu
Y
Liu
Ying
Y
Wang
Feng
F
Pan
Liyun
L
Qiu
Aili
A
Guo
Hong
H
Lv
Pingbo
P
Yao
Nan
N
Zhang
Ping
P
Wang
D056151:Airway Remodeling / Q000187:drug effects*; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D020397:Goblet Cells / Q000187:drug effects / Q000502:physiology; D006629:Hirudins / Q000494:pharmacology; D009093:Mucus; D010047:Ovalbumin / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D044463:Receptor, PAR-1 / Q000235:genetics / Q000378:metabolism*; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
D006629:Hirudins; D044463:Receptor, PAR-1; D053773:Transforming Growth Factor beta1; D010047:Ovalbumin; D003094:Collagen; D013917:Thrombin