title: Idiopathic Pulmonary Fibrosis: A Genetic Disease That Involves Mucociliary Dysfunction of the Peripheral Airways.
abstract: Idiopathic pulmonary fibrosis (IPF) is an incurable complex genetic disorder that is associated with sequence changes in 7 genes (MUC5B, TERT, TERC, RTEL1, PARN, SFTPC, and SFTPA2) and with variants in at least 11 novel loci. We have previously found that 1) a common gain-of-function promoter variant in MUC5B rs35705950 is the strongest risk factor (genetic and otherwise), accounting for 30-35% of the risk of developing IPF, a disease that was previously considered idiopathic; 2) the MUC5B promoter variant can potentially be used to identify individuals with preclinical pulmonary fibrosis and is predictive of radiologic progression of preclinical pulmonary fibrosis; and 3) MUC5B may be involved in the pathogenesis of pulmonary fibrosis with MUC5B message and protein expressed in bronchiolo-alveolar epithelia of IPF and the characteristic IPF honeycomb cysts. Based on these considerations, we hypothesize that excessive production of MUC5B either enhances injury due to reduced mucociliary clearance or impedes repair consequent to disruption of normal regenerative mechanisms in the distal lung. In aggregate, these novel considerations should have broad impact, resulting in specific etiologic targets, early detection of disease, and novel biologic pathways for use in the design of future intervention, prevention, and mechanistic studies of IPF.
authors.affiliation: Department of Medicine, University of Colorado Denver, School of Medicine, Aurora, Colorado; National Jewish Health, Denver, Colorado; and Department of Immunology, University of Colorado Denver, School of Medicine, Aurora, Colorado.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Evans
authors.affiliation: Department of Medicine, University of Colorado Denver, School of Medicine, Aurora, Colorado; National Jewish Health, Denver, Colorado; and Department of Immunology, University of Colorado Denver, School of Medicine, Aurora, Colorado.
authors.forename: Tasha E
authors.initials: TE
authors.lastname: Fingerlin
authors.affiliation: Department of Medicine, University of Colorado Denver, School of Medicine, Aurora, Colorado; National Jewish Health, Denver, Colorado; and Department of Immunology, University of Colorado Denver, School of Medicine, Aurora, Colorado.
authors.forename: Marvin I
authors.initials: MI
authors.lastname: Schwarz
authors.affiliation: Department of Medicine, University of Colorado Denver, School of Medicine, Aurora, Colorado; National Jewish Health, Denver, Colorado; and Department of Immunology, University of Colorado Denver, School of Medicine, Aurora, Colorado.
authors.forename: David
authors.initials: D
authors.lastname: Lynch
authors.affiliation: Department of Medicine, University of Colorado Denver, School of Medicine, Aurora, Colorado; National Jewish Health, Denver, Colorado; and Department of Immunology, University of Colorado Denver, School of Medicine, Aurora, Colorado.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kurche
authors.affiliation: Department of Medicine, University of Colorado Denver, School of Medicine, Aurora, Colorado; National Jewish Health, Denver, Colorado; and Department of Immunology, University of Colorado Denver, School of Medicine, Aurora, Colorado.
authors.forename: Laura
authors.initials: L
authors.lastname: Warg
authors.affiliation: Department of Medicine, University of Colorado Denver, School of Medicine, Aurora, Colorado; National Jewish Health, Denver, Colorado; and Department of Immunology, University of Colorado Denver, School of Medicine, Aurora, Colorado.
authors.forename: Ivana V
authors.initials: IV
authors.lastname: Yang
authors.affiliation: Department of Medicine, University of Colorado Denver, School of Medicine, Aurora, Colorado; National Jewish Health, Denver, Colorado; and Department of Immunology, University of Colorado Denver, School of Medicine, Aurora, Colorado.
authors.forename: David A
authors.initials: DA
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D055745:Bronchioles / Q000503:physiopathology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics* / Q000503:physiopathology; D055257:Mucin-5B / Q000235:genetics*; D009079:Mucociliary Clearance / Q000235:genetics*; D011650:Pulmonary Alveoli / Q000503:physiopathology*; D020545:Respiratory Mucosa / Q000503:physiopathology
chemical_list: C524578:MUC5B protein, human; D055257:Mucin-5B