Effect of SIS3 on Extracellular Matrix Remodeling and Repair in a Lipopolysaccharide-Induced ARDS Rat Model.
Effect of SIS3 on Extracellular Matrix Remodeling and Repair in a Lipopolysaccharide-Induced ARDS Rat Model.
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SIS3 对脂多糖诱导的 ARDS 大鼠模型细胞外基质重塑和修复的影响。
DOI：
10.1155/2020/6644687
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发表时间：
2020
影响因子：
4.1
通讯作者：
Pinhu L
中科院分区：
文献类型：
--
作者：
Liang Q;Lin Q;Li Y;Luo W;Huang X;Jiang Y;Qin C;Nong J;Chen X;Sooranna SR;Pinhu L
细胞外基质(ECM)在以肺损伤为特征的急性呼吸窘迫综合征(ARDS)的发生发展过程中起着重要作用。尽管转化生长因子-Smad1可以通过Smad3等细胞内信号分子调节细胞外基质的表达，但其作为急性呼吸窘迫综合征治疗靶点的作用尚不清楚。本研究通过气管内注入脂多糖(LPS)建立了一种模拟ARDS的大鼠模型。模型组大鼠腹腔注射选择性Smad3抑制剂(SIS3)，对照组注射磷酸盐缓冲液(PBS)。然后用组织学分析、免疫组织化学、RT-qPCR、ELISA法和Western blotting对动物组织进行评估。脂多糖可刺激模型大鼠RAGE、转化生长因子β1、MMP2和MMP9的表达。此外，观察到SIS3处理可以逆转这些分子的表达。此外，SIS3可部分抑制Smad3的磷酸化，减轻包括肺损伤和肺水肿在内的症状。这些结果表明，SIS3或阻断转化生长因子-β/Smad3通路可以影响细胞外基质的重塑，这可能是一种治疗急性呼吸窘迫综合征的策略。
The remodeling of the extracellular matrix (ECM) in the parenchyma plays an important role in the development of acute respiratory distress syndrome (ARDS), a disease characterized by lung injury. Although it is clear that TGF-β1 can modulate the expression of the extracellular matrix (ECM) through intracellular signaling molecules such as Smad3, its role as a therapeutic target against ARDS remains unknown. In this study, a rat model was established to mimic ARDS via intratracheal instillation of lipopolysaccharide (LPS). A selective inhibitor of Smad3 (SIS3) was intraperitoneally injected into the disease model, while phosphate-buffered saline (PBS) was used in the control group. Animal tissues were then evaluated using histological analysis, immunohistochemistry, RT-qPCR, ELISA, and western blotting. LPS was found to stimulate the expression of RAGE, TGF-β1, MMP2, and MMP9 in the rat model. Moreover, treatment with SIS3 was observed to reverse the expression of these molecules. In addition, pretreatment with SIS3 was shown to partially inhibit the phosphorylation of Smad3 and alleviate symptoms including lung injury and pulmonary edema. These findings indicate that SIS3, or the blocking of TGF-β/Smad3 pathways, could influence remodeling of the ECM and this may serve as a therapeutic strategy against ARDS.
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影响因子：
6.9
作者：
Houghton, A. McGarry
通讯作者：
Houghton, A. McGarry
影响因子：
3.6
作者：
Jinnin, M;Ihn, H;Tamaki, K
通讯作者：
Tamaki, K
大豆黄酮通过 Toll 样受体 4/NF-kappaB 途径减轻脂多糖诱导的急性肺损伤。
影响因子：
5.6
作者：
Feng, Guang;Sun, Bo;Li, Tian-zuo
通讯作者：
Li, Tian-zuo
DOI：
10.1152/ajplung.00023.2011
发表时间：
2011-04-01
影响因子：
4.9
作者：
Hergrueter, Anja H.;Nguyen, Khoi;Owen, Caroline A.
通讯作者：
Owen, Caroline A.
影响因子：
10
作者：
Calfee, C. S.;Ware, L. B.;Matthay, M. A.
通讯作者：
Matthay, M. A.