Department of Pediatrics, Jinan Central Hospital Affiliated to Shandong Univeristy, Jinan, China.
Inhal Toxicol. 2013 Aug;25(10):577-86. doi: 10.3109/08958378.2013.813995.
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.
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.
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.
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.
蛋白酶激活受体-1（PAR-1）广泛分布于血小板中，参与由凝血酶激活的凝血级联反应。在本研究中，我们旨在探讨 PAR-1 在凝血酶诱导转化生长因子-β1（TGF-β1）促进卵清蛋白（OVA）致敏大鼠气道重塑过程中的作用。
通过全身致敏和反复OVA 激发建立慢性哮喘大鼠模型。各实验组的凝血酶、重组水蛭素、PAR-1 抑制剂 ER-112780-06 的剂量有所不同。我们评估了这些组中支气管肺泡灌洗液（BALF）中的凝血酶浓度。评估了 PAR-1 的蛋白和基因表达，同时也检测了 TGF-β1 的表达。
哮喘大鼠气道中的 PAR-1 mRNA 水平和蛋白水平均高于正常大鼠，经凝血酶处理后明显升高，经凝血酶抑制剂处理后则降低。凝血酶可增强气道重塑，而凝血酶抑制剂和 PAR-1 拮抗剂则可减弱气道重塑。凝血酶处理可显著增加哮喘大鼠 TGF-β1 蛋白的表达，而凝血酶抑制剂和 PAR-1 拮抗剂处理则可降低其表达。
PAR-1 的表达受凝血酶调节，凝血酶诱导 TGF-β1 的表达，通过 PAR-1 促进 OVA 致敏大鼠的气道重塑。
