TGF-β1 induces progressive pleural scarring and subpleural fibrosis
TGF-β1 induces progressive pleural scarring and subpleural fibrosis
复制标题
DOI：
10.4049/jimmunol.179.9.6043
复制
发表时间：
2007-11-01
影响因子：
4.4
通讯作者：
Bonniaud, Philippe
中科院分区：
文献类型：
--
作者：
Decologne, Nathalie;Kolb, Martin;Bonniaud, Philippe
胸膜纤维化是一种被误解的疾病，可导致严重的限制性肺部疾病，发病率高，甚至死亡。这种情况可因多种疾病和组织损伤而发展，其中包括传染病、石棉、药物和放射治疗。目前还没有有效的治疗方法来逆转已建立的胸膜纤维化。转化生长因子-β1被怀疑是这一过程中的一个关键细胞因子，即使没有得到证实。在本研究中，我们利用腺病毒将转化生长因子-β1基因转移到大鼠胸膜间皮细胞。我们发现局部和短暂的转化生长因子-β1的过度表达导致同质性的、长期的和进行性的胸膜纤维化，而不是胸膜粘连，并伴随着严重的肺功能损害。我们进一步证明，胸膜纤维化可以从内脏层扩展到肺实质，但不能从壁层扩展到肌肉。我们提供的证据表明，实质内的基质堆积和纤维化是通过“间皮-成纤维细胞样转化”的过程而演变的，并提示胸膜间皮细胞可能参与了胸膜下分布模式的发展，而胸膜下分布模式是肺纤维化的标志。这一新的胸膜纤维化模型将使我们更好地了解进行性纤维化的机制，并探索胸膜腔内新的抗纤维化治疗方法。
Pleural fibrosis is a misunderstood disorder which can cause severe restrictive lung disease with high morbidity and even mortality. The condition can develop in response to a large variety of diseases and tissue injury, among them infectious disease, asbestos, drugs, and radiation therapy. There is no efficient treatment to reverse established pleural fibrosis. TGF-beta 1 is suspected, even if not proven, as a key cytokine in this process. In this study, we used adenoviral gene transfer of TGF-beta 1 to the pleural mesothelium in rats. We show that local and transient TGF-beta 1 overexpression induces homogenous, prolonged, and progressive pleural fibrosis without pleurodesis, associated with severe impairment of pulmonary function. We further demonstrate that pleural fibrosis can expand into the lung parenchyma from the visceral layer, but not into the muscle from the parietal layer. We provide evidence that matrix accumulation and fibrosis within the parenchyma evolved through a process involving "mesothelial-fibroblastoid transformation" and suggest that the pleural mesothelial cell may be an important player involved in the development of the subpleural distribution pattern known to be a hallmark of pulmonary fibrosis. This new model of pleural fibrosis will allow us to better understand the mechanisms of progressive fibrogenesis, and to explore novel antifibrotic therapies in the pleural cavity.