Idiopathic pulmonary fibrosis (IPF) is a debilitating chronic progressive and fibrosing lung disease that culminates in the destruction of alveolar integrity and dismal prognosis. Its etiology is unknown and pathophysiology remains unclear. While great advances have been made in elucidating the pathogenesis mechanism, considerable gaps related to information on pathogenetic pathways and key protein targets involved in the clinical course of the disease exist. These issues need to be addressed for better clinical management of this highly challenging disease. Omics approach has revolutionized the entire area of disease understanding and holds promise in its translation to clinical biomarker discovery. This review outlines the contribution of proteomics towards identification of important biomarkers in IPF in terms of their clinical utility, i.e. prognosis, differential diagnosis, disease progression and treatment monitoring. The major dysregulated pathways associated with IPF are also discussed. Based on numerous proteomics studies on human and animal models, it is proposed that IPF pathogenesis involves complex interactions of several pathways such as oxidative stress, endoplasmic reticulum stress, unfolded protein response, coagulation system, inflammation, abnormal wounding, fibroblast proliferation, fibrogenesis and deposition of extracellular matrix. These pathways and their key path-changing mediators need further validation in large well-planned multi-centric trials at various geographical locations for successful development of clinical biomarkers of this confounding disease.

中文翻译：

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特发性肺纤维化的蛋白质组学：对生物标志物的探索

特发性肺纤维化 (IPF) 是一种使人衰弱的慢性进行性和纤维化肺病，最终导致肺泡完整性破坏和预后不佳。其病因不明，病理生理学仍不清楚。虽然在阐明发病机制方面取得了很大进展，但与疾病临床过程中涉及的致病途径和关键蛋白质靶点的信息相关的信息存在相当大的差距。为了更好地临床管理这种极具挑战性的疾病，需要解决这些问题。组学方法彻底改变了疾病理解的整个领域，并有望将其转化为临床生物标志物的发现。本综述概述了蛋白质组学对鉴定 IPF 中重要生物标志物的临床效用的贡献，即预后、鉴别诊断、疾病进展和治疗监测。还讨论了与 IPF 相关的主要失调途径。基于对人和动物模型的大量蛋白质组学研究，提出 IPF 发病机制涉及多种途径的复杂相互作用，例如氧化应激、内质网应激、未折叠蛋白反应、凝血系统、炎症、异常创伤、成纤维细胞增殖、纤维生成和沉积细胞外基质。这些途径及其关键的路径改变介质需要在不同地理位置的大型精心计划的多中心试验中进一步验证，以成功开发这种混杂疾病的临床生物标志物。