The leading role of epithelial cells in the pathogenesis of idiopathic pulmonary fibrosis
The leading role of epithelial cells in the pathogenesis of idiopathic pulmonary fibrosis
复制标题
DOI：
10.1016/j.cellsig.2019.109482
复制
发表时间：
2020-02-01
影响因子：
4.8
通讯作者：
Pardo, Annie
中科院分区：
文献类型：
--
作者：
Selman, Moises;Pardo, Annie
特发性肺纤维化（IPF）是一种病因不明的持续进行性和破坏性间质性肺疾病，其中正常的肺结构丧失并被纤维化组织取代，导致不可逆和进行性呼吸功能不全。历史上，IPF被认为是一种慢性炎症性疾病，逐渐进展为既定的纤维化。然而，强有力的临床和实验证据表明，该疾病代表上皮驱动的疾病，其由遗传和环境风险因素、衰老相关过程和促纤维化表观遗传重编程的复杂相互作用引起。这些因素的聚集导致上皮细胞的异常激活，从而引发疾病的发展，产生几乎所有参与成纤维细胞迁移、增殖和激活、分化为肌成纤维细胞以及细胞外基质过度和混乱分泌的介质。蛋白质。虽然在了解远端气道和肺泡上皮细胞的这种异常行为的原因和后果方面取得了进展，但启动和维持上皮细胞与成纤维细胞和其他驻留细胞之间的多向异常通信的恶性循环的机制尚未阐明。在这篇综述中，我们讨论了上皮细胞的作用以及特发性肺纤维化反应的机制，并强调了这些细胞的一些有希望的治疗靶点。
Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive and devastating interstitial lung disease of unknown etiology, where the normal lung architecture is lost and replaced by fibrotic tissue leading to an irreversible and progressive respiratory insufficiency. Historically, IPF was considered a chronic inflammatory disorder, which gradually progressed to established fibrosis. However, strong clinical and experimental evidence indicates that the disease represents an epithelial-driven disorder which results from a complex interplay of genetic and environmental risk factors, aging-associated processes and a profibrotic epigenetic reprogramming. The convergence of these factors results in the aberrant activation of epithelial cells that initiate the development of the disease, producing virtually all the mediators that participate in the migration, proliferation and activation of fibroblasts, their differentiation to myofibroblasts and the excessive and chaotic secretion of extracellular matrix proteins. Although progress has been made in understanding the causes and consequences of this abnormal behavior of distal airways and alveolar epithelium, the mechanisms that initiate and perpetuate the vicious circle of multidirectional abnormal communications between the epithelium and fibroblasts and other resident cells have not been elucidated. In this review, we discuss the role of epithelial cells and the mechanisms underlying the fibrotic response in IPF, and highlight some promising therapeutic targets for these cells.