Noninvasive monitoring of pulmonary fibrosis by targeting matrix metalloproteinases (MMPs).
Noninvasive monitoring of pulmonary fibrosis by targeting matrix metalloproteinases (MMPs).
复制标题
通过靶向基质金属蛋白酶 (MMP) 对肺纤维化进行无创监测。
DOI：
10.1021/mp300613x
复制
发表时间：
2013-06-03
影响因子：
4.9
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Cai Y;Zhu L;Zhang F;Niu G;Lee S;Kimura S;Chen X
虽然特发性肺纤维化（PF）是一种毁灭性的肺部疾病，但PF的管理（包括有效监测疾病进展）仍然是一项挑战。在此，我们介绍了一种新的，快速，超灵敏的金属蛋白酶（MMP）激活的光学探针，命名为MMP-P12，非侵入性监测PF的进展和PF治疗的反应。博莱霉素（BLM）诱导的小鼠PF模型进行非侵入性光学成像在不同的时间点后，BLM治疗。在21天的实验期间，小鼠PF模型发展成纤维化，并且PF的进展与MMP-2表达的逐步增加具有良好的相关性，如通过定量RT-PCR和Western印迹分析在给药后7天、14天和21天检测的。在这些天，MMP激活的荧光图像在体内和离体采集。信号定量显示荧光信号的时间依赖性肺特异性增量增加。作为PF的治疗，从BLM施用的第七天开始，每天静脉内施用分泌珠蛋白3A 2，持续五天，这导致MMP-2活性降低和PF减少，如先前所证明的。重要的是，反映MMP活性的荧光信号强度也降低。总之，MMPs可能在PF的发展中发挥重要作用，MMP-P12探针可能是PF检测的一个有前途的工具，即使是在疾病的早期阶段，也是治疗反应的指标。
While idiopathic pulmonary fibrosis (PF) is a devastating lung disease, the management of PF including effective monitoring of disease progression remains a challenge. Herein, we introduce a novel, fast, and ultrasensitive metalloproteinase (MMP) activatable optical probe, named MMP-P12, to noninvasively monitor PF progression and response to PF treatment. A bleomycin (BLM)-induced mouse PF model was subjected noninvasively to optical imaging at various time points after BLM treatment. The mouse PF model developed fibrosis during 21 days of experimental period, and the progression of PF was well correlated with the stepwise increase of MMP-2 expression as examined by quantitative RT-PCR and Western blot analysis on the 7-, 14-, and 21-day post-BLM administration. On these days, MMP-activated fluorescence images were acquired in vivo and ex vivo. Signal quantification showed time-dependent lung-specific incremental increases in fluorescence signals. As a treatment for PF, secretoglobin 3A2 was daily administered intravenously for five days starting on day seven of BLM administration, which resulted in reduced MMP-2 activity and reduction of PF as previously demonstrated. Importantly, the fluorescence signal that reflected MMP activity also decreased in intensity. In conclusion, MMPs may play an important role in PF development and the MMP-P12 probe could be a promising tool for PF detection, even at an early stage of the disease as well as an indicator of therapy response.
登录
查看更多内容
影响因子：
12.4
作者：
Choi KY;Swierczewska M;Lee S;Chen X
通讯作者：
Chen X
影响因子：
1.3
作者：
Lee, HJ;Im, JG;Yeon, KM
通讯作者：
Yeon, KM
影响因子：
12.4
作者：
Habibollahi P;Figueiredo JL;Heidari P;Dulak AM;Imamura Y;Bass AJ;Ogino S;Chan AT;Mahmood U
通讯作者：
Mahmood U
影响因子：
12.4
作者：
Jang B;Choi Y
通讯作者：
Choi Y
影响因子：
10.8
作者：
Cha, Eui-Joon;Jang, Eue Soon;Ahn, Cheol-Hee
通讯作者：
Ahn, Cheol-Hee