Proteomics in idiopathic pulmonary fibrosis: the quest for biomarkers

摘要

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