Prostaglandin E2 and the Pathogenesis of Pulmonary Fibrosis
Prostaglandin E2 and the Pathogenesis of Pulmonary Fibrosis
复制标题
DOI：
10.1165/rcmb.2011-0025rt
复制
发表时间：
2011-09-01
影响因子：
6.4
通讯作者：
Moore, Bethany B.
中科院分区：
文献类型：
--
作者：
Bozyk, Paul D.;Moore, Bethany B.
前列腺素（PG）E-2是一种生物活性类花生酸，调节许多生物学上重要的过程，部分原因是它能够通过四种不同的G蛋白偶联受体发出信号，这些受体在不同的细胞类型中具有不同的信号传导活性和独特的表达模式。尽管PGE（2）与许多器官的恶性肿瘤有关，但人们认为它在纤维化肺病的发生中起着有益的作用。这在一定程度上是由于PGE（2）能够限制肺成纤维细胞和肌成纤维细胞的许多病理生物学特征，包括PGE（2）限制成纤维细胞增殖、迁移、胶原蛋白分泌的能力，以及正如我们最初在《杂志》上报道的那样2003年，限制转化生长因子（TGF）-β诱导的肌成纤维细胞分化的能力。在肺纤维化的情况下，PGE（2）的产生和信号传导通常会减少。在过去的8年中，已经取得了重大进展，以更好地了解PGE（2）的生产和信号在肺纤维化的设置失调。我们也有一个更清晰的图片如何PGE（2）抑制肌成纤维细胞分化和受体信号通路，可以影响成纤维细胞增殖。本综述强调了这些最新进展，并对PGE（2）及其下游信号可以调节的潜在方式提供了新的见解，以在没有有效治疗方案的疾病中获得治疗益处。
Prostaglandin (PG)E-2 is a bioactive eicosanoid that regulates many biologically important processes in part due to its ability to signal through four distinct G-protein-coupled receptors with differential signaling activity and unique expression patterns in different cell types. Although PGE(2) has been linked to malignancy in manyorgans, it is believed to play a beneficial role in the setting of fibrotic lung disease. This is in part due to the ability of PGE(2) to limit many of the pathobiologic features of lung fibroblasts and myofibroblasts, including the ability of PGE(2) to limit fibroblast proliferation, migration, collagen secretion, and, as originally reported in the Journal by us in 2003, the ability to limit transforming growth factor (TGF)-beta-induced myofibroblast differentiation. In the setting of lung fibrosis, PGE(2) production and signaling is often diminished. In the last 8 years, significant advances have been made to better understand the dysregulation of PGE(2) production and signaling in the setting of lung fibrosis. We also have a clearer picture of how PGE(2) inhibits myofibroblast differentiation and the receptor signaling pathways that can influence fibroblast proliferation. This review highlights these recent advances and offers new insights into the potential ways that PGE(2) and its downstream signals can be regulated for therapeutic benefit in a disease that has no validated treatment options.