Mechanisms of alveolar epithelial injury, repair, and fibrosis.
Mechanisms of alveolar epithelial injury, repair, and fibrosis.
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DOI：
10.1513/annalsats.201410-448mg
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发表时间：
2015-03-01
影响因子：
8.3
通讯作者：
Mercer, Paul F
中科院分区：
文献类型：
--
作者：
Chambers, Rachel C;Mercer, Paul F
许多纤维化肺疾病面临的挑战是，这些病症通常出现较晚，通常是在几十年的重复性肺泡上皮损伤之后，在此期间，功能性肺泡单位逐渐消失并被无功能性结缔组织取代。由此产生的纤维化通常是进行性的，在特发性肺纤维化（IPF）的情况下，总是会导致呼吸功能不全，并最终导致受影响个体过早死亡。近年来，人们越来越认识到慢性炎症作为纤维化反应驱动因素的相对重要性。目前的证据表明，IPF 是由于遗传易感人群和老年人的重复性上皮损伤和高度异常的伤口愈合反应而引起的。非特异性抗炎药没有临床益处，但适应不良的免疫反应在决定结果中的潜在贡献正在获得越来越多的认识。年轻人与老年人组织再生潜力的关键差异的重要性也开始得到更充分的认识。此外，组织修复和癌症的机制存在相当大的重叠，IPF 患者患肺癌的风险更高。因此，进行性纤维化和癌症可能代表了组织损伤反应高度失调的极端情况。这篇简短的综述重点关注其中的一些证据，以及我们目前对 IPF 特定背景下慢性上皮损伤后异常组织修复反应的理解。
The challenge facing many fibrotic lung diseases is that these conditions usually present late, often after several decades of repetitive alveolar epithelial injury, during which functional alveolar units are gradually obliterated and replaced with nonfunctional connective tissue. The resulting fibrosis is often progressive and, in the case of idiopathic pulmonary fibrosis (IPF), invariably leads to respiratory insufficiency and, ultimately, the premature death of affected individuals. Recent years have seen a greater appreciation of the relative importance of chronic inflammation as a driver of fibrotic responses. Current evidence suggests that IPF arises as a result of repetitive epithelial injury and a highly aberrant wound healing response in genetically susceptible and aged individuals. Nonspecific anti-inflammatory agents offer no clinical benefit, but the potential contribution of maladaptive immune responses in determining outcome is gaining increasing recognition. The importance of key differences in the tissue-regenerative potential in young versus aged individuals is also beginning to be more fully appreciated. Moreover, there is considerable overlap in the mechanisms underlying tissue repair and cancer, and patients with IPF are at heightened risk of developing lung cancer. Progressive fibrosis and cancer may therefore represent the extremes of a highly dysregulated tissue injury response. This brief review focuses on some of this evidence and on our current understanding of abnormal tissue repair responses after chronic epithelial injury in the specific context of IPF.