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.

中文翻译：

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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

实质中细胞外基质 (ECM) 的重塑在急性呼吸窘迫综合征 (ARDS) 的发展中起着重要作用，ARDS 是一种以肺损伤为特征的疾病。虽然很明显 TGF- β1 可以通过细胞内信号分子如 Smad3 调节细胞外基质 (ECM) 的表达，其作为 ARDS 治疗靶点的作用仍然未知。在本研究中，通过气管内滴注脂多糖 (LPS) 建立了模拟 ARDS 的大鼠模型。Smad3的选择性抑制剂（SIS3）被腹腔注射到疾病模型中，而磷酸盐缓冲盐水（PBS）被用于对照组。然后使用组织学分析、免疫组织化学、RT-qPCR、ELISA 和蛋白质印迹法评估动物组织。发现 LPS 可刺激 RAGE、TGF- β的表达1、MMP2和MMP9在大鼠模型中。此外，观察到用 SIS3 处理逆转这些分子的表达。此外，SIS3 预处理显示部分抑制 Smad3 的磷酸化并减轻包括肺损伤和肺水肿在内的症状。这些发现表明 SIS3 或 TGF- β /Smad3 通路的阻断可能影响 ECM 的重塑，这可能作为针对 ARDS 的治疗策略。