Release of biologically active TGF-β from airway smooth muscle cells induces autocrine synthesis of collagen
Release of biologically active TGF-β from airway smooth muscle cells induces autocrine synthesis of collagen
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DOI：
10.1152/ajplung.2001.280.5.l999
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发表时间：
2001-05-01
影响因子：
4.9
通讯作者：
Khalil, N
中科院分区：
文献类型：
--
作者：
Coutts, A;Chen, G;Khalil, N
在严重或慢性哮喘中，气道平滑肌细胞（ASMC）质量增加以及气道平滑肌层结缔组织蛋白增加。转化生长因子- β (tgf - β)在哺乳动物中存在三种亚型，是结缔组织蛋白合成的有效调节剂。利用免疫组织化学，我们之前已经证明asmc含有大量的tgf - β - 1-3。在这项研究中，我们证明了牛asmc来源的tgf - β与tgf - β潜伏期结合蛋白1 （LTBP-1）在相同细胞中表达相关。与LTBP-1相关的tgf - β定位于细胞外。此外，纤溶酶（一种丝氨酸蛋白酶）调节asmc分泌具有生物活性形式的tgf - β以及细胞外tgf - β的释放。纤溶酶释放的生物活性tgf - β诱导ASMCs自分泌合成I型胶原。ASMCs自分泌诱导胶原表达可能导致一些哮喘患者气道的不可逆纤维化和重塑。
In severe or chronic asthma, there is an increase in airway smooth muscle cell (ASMC) mass as well as an increase in connective tissue proteins in the smooth muscle layer of airways. Transforming growth factor-beta (TGF-beta) exists in three isoforms in mammals and is a potent regulator of connective tissue protein synthesis. Using immunohistochemistry, we had previously demonstrated that ASMCs contain large quantities of TGF-beta1-3. In this study, we demonstrate that bovine ASMC-derived TGF-beta associates with the TGF-beta latency binding protein-1 (LTBP-1) expressed by the same cells. The TGF-beta associated with LTBP-1 localizes TGF-beta extracellularly. Furthermore, plasmin, a serine protease, regulates the secretion of a biologically active form of TGF-beta by ASMCs as well as the release of extracellular TGF-beta. The biologically active TGF-beta released by plasmin induces ASMCs to synthesize collagen I in an autocrine manner. The autocrine induction of collagen expression by ASMCs may contribute to the irreversible fibrosis and remodeling seen in the airways of some asthmatics.