Idiopathic Pulmonary Fibrosis, a Disease Initiated by Mucociliary Dysfunction

Abstract

The overarching goal of this Program is to develop the scientific knowledge needed to predict and prevent the progression of IPF. We postulate that IPF is caused by recurrent injury/repair/regeneration at the bronchoalveolar junction secondary to overexpression of MUC5B, mucociliary dysfunction, retention of particles, ER stress, and disruption of normal reparative and regenerative mechanisms in the distal lung. During the first year of funding, we have (1) obtained local and DoD approvals for human and animal research; (2) enrolled 26 first degree relatives of individuals with IPF and completed all study procedures for Project 1; (3) performed ChIP, MNase, and TF binding assays to show that MUC5B promoter region is hyperchippable and that HIF1 and GCF bind in this region (Project 2); (4) imported and bred new strains of mice (St3gal3, Fut2, Ern2, Ift88, andArl13b) in Projects 3 and 4; (5) developed and assessed the amounts and glycosylation of Muc5b in mouse models at baseline, and identified changes in polymer size and migration after inflammatory challenge (Project 3).

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2018
Accession Number
AD1093887

Entities

People

  • Anthony N Gerber
  • Christopher M Evans
  • David A Schwartz
  • Ivana Yang
  • Sean P Colgan
  • Tasha Fingerlin

Organizations

  • Regents of the University of Colorado

Tags

DTIC Thesaurus Topics

  • Biostatistics
  • Cell Line
  • Cells
  • Culture Techniques
  • Data Analysis
  • Data Storage Systems
  • Department Of Defense
  • Dysfunction
  • Gene Expression
  • Genetics
  • Institutional Review Board
  • Lung Diseases
  • Medical Personnel
  • Statistical Analysis
  • Stem Cells
  • Three Dimensional
  • X-Ray Computed Tomography

Fields of Study

  • Biology

Readers

  • Clinical Trial Research.
  • Immunology and Pathology
  • Molecular Biology and Genetics