Tryptase and agonists of PAR-2 induce the proliferation of human airway smooth muscle cells
Tryptase and agonists of PAR-2 induce the proliferation of human airway smooth muscle cells
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DOI：
10.1152/jappl.2001.91.3.1372
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发表时间：
2001-09-01
影响因子：
3.3
通讯作者：
Walls, AF
中科院分区：
文献类型：
--
作者：
Berger, P;Perng, DW;Walls, AF
气道重塑伴平滑肌细胞（SMC）增生是慢性哮喘的特征。我们研究了类胰蛋白酶，人肥大细胞的主要分泌产物，作为人气道平滑肌细胞的生长因子的潜力。由于这种丝氨酸蛋白酶可以激活蛋白酶激活受体-2（PAR-2），我们还研究了PAR-2的肽激动剂SLIGKV的作用。与肺类胰蛋白酶孵育引起[H-3]胸苷掺入增加一倍，当我们使用MTS试验时，发现细胞数量增加相似。该效应是催化位点依赖性的，被蛋白酶抑制剂亮抑酶肽和苯甲脒以及酶的热灭活所废除。用百日咳毒素、calphostin C或染料木黄酮预孵育细胞，可抑制胰蛋白酶诱导的DNA合成。因此，转导机制可能涉及百日咳毒素敏感的G蛋白、蛋白激酶C和酪氨酸激酶。SLIGKV在SMC上引起类似于类胰蛋白酶的反应。类胰蛋白酶可能通过作用于PAR-2而促进哮喘气道平滑肌细胞增殖。
Airway remodeling with smooth muscle cell (SMC) hyperplasia is a feature of chronic asthma. We investigated the potential for tryptase, the major secretory product of human mast cells, to act as a growth factor for human airway SMCs. Because this serine protease can activate proteinase-activated receptor-2 (PAR-2), we also examined the actions of SLIGKV, a peptide agonist of PAR-2. Incubation with lung tryptase provoked a twofold increase in [H-3] thymidine incorporation; a similar increase in cell numbers was found when we used the MTS assay. The effect was catalytic site dependent, being abolished by the protease inhibitors leupeptin and benzamidine and by heat inactivation of the enzyme. Tryptase-induced DNA synthesis was inhibited by preincubation of the cells with pertussis toxin, calphostin C, or genistein. Transduction mechanisms are thus likely to involve a pertussis toxin-sensitive G protein, protein kinase C, and tyrosine kinase. SLIGKV elicited a response on SMCs similar to that of tryptase. Tryptase could provide an important stimulus for SMC proliferation in asthmatic airways, by acting on PAR-2.