TY - T1的组织蛋白酶B促进胶原蛋白合成,使闭塞性细支气管炎综合征JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.01416 -2020欧元六世- 57 - 5 SP - 2001416 AU -莫龙,卡梅拉盟——Smirnova纳塔莉亚f . AU - Jeridi,艾莎盟——Kneidinger尼古拉斯盟——Hollauer鳌,思楚普Jonas Christian AU - Kaminski, Naftali AU - Jenne, Dieter AU - Eickelberg, Oliver AU - Yildirim, Ali Önder Y1 - 2011/05/01 UR - //www.qdcxjkg.com/content/57/5/2001416.abstract N2 -闭塞性细支气管炎综合征(BOS)是肺移植(LTx)后的主要并发症。BOS的特点是大量支气管周围纤维化，导致空气滞留诱导肺功能障碍。组织蛋白酶B是一种溶酶体半胱氨酸蛋白酶，已被证明在几种疾病中加强纤维化途径。然而，组织蛋白酶B在BOS进展中的相关性尚未得到解决。本研究旨在阐明组织蛋白酶B在BOS发病机制中的作用。我们测定了支气管肺泡灌洗液(BALF)和来自健康供体(HD)和BOS LTx患者的肺组织中的组织蛋白酶B水平。采用荧光共振能量转移法检测组织蛋白酶B活性，采用Western blotting、ELISA和免疫染色法检测蛋白表达。为了研究组织蛋白酶B在BOS病理生理中的作用，我们使用了左LTx小鼠模型。利用巨噬细胞和成纤维细胞进行体外机制研究。We found a significant increase of cathepsin B activity in BALF and lung tissue from BOS patients, as well as in our murine model of lymphocytic bronchiolitis. Moreover, cathepsin B activity was associated with increased biosynthesis of collagen and had a negative effect on lung function. We observed that cathepsin B was mainly expressed in macrophages that infiltrated areas characterised by a massive accumulation of collagen deposition. Mechanistically, macrophage-derived cathepsin B contributed to transforming growth factor-β1-dependent activation of fibroblasts, and its inhibition reversed the phenotype.Infiltrating macrophages release active cathepsin B, thereby promoting fibroblast activation and subsequent collagen deposition, which drive BOS. Cathepsin B represents a promising therapeutic target to prevent the progression of BOS.CatB is a new biomarker and therapeutic target for early bronchiolitis obliterans syndrome after lung transplantation https://bit.ly/36vOXHc ER -