Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicineand.
Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee.
Am J Med Sci. 2019 May;357(5):374-378. doi: 10.1016/j.amjms.2019.01.010. Epub 2019 Jan 22.
Idiopathic pulmonary fibrosis is a disease of older adults leading to progressive dyspnea and reduced exercise capacity, typically resulting in death within 3-5years of diagnosis. Underlying genetic susceptibility combined with environmental insults is proposed to trigger a chronic wound repair response, leading to activation of the fibrotic cascade. Perturbations in several molecular pathways mediate vulnerability of the alveolar epithelium to injurious agents, including the unfolded protein response, autophagy, mitophagy, and cellular senescence. These cellular responses are intricately intertwined and link genetic susceptibility to the progressive fibrotic phenotype. Ongoing studies investigating these pathways in type II alveolar epithelial cells show promise for identifying new targeted interventions that could prevent or halt the progression of IPF.
特发性肺纤维化是一种老年疾病，导致进行性呼吸困难和运动能力下降，通常在诊断后 3-5 年内导致死亡。据推测，潜在的遗传易感性加上环境因素的刺激会引发慢性伤口修复反应，导致纤维化级联的激活。几个分子途径的紊乱介导了肺泡上皮对损伤因子的易感性，包括未折叠蛋白反应、自噬、线粒体自噬和细胞衰老。这些细胞反应错综复杂地交织在一起，将遗传易感性与进行性纤维化表型联系起来。目前正在研究这些途径在 II 型肺泡上皮细胞中的作用，有望为确定新的靶向干预措施提供依据，这些措施可能预防或阻止 IPF 的进展。
