# The role of multiciliated cell dysfunction in pathogenesis of IPF

> **NIH NIH F32** · UNIVERSITY OF COLORADO DENVER · 2020 · $67,446

## Abstract

Project Summary/ Abstract
 The goal of this proposal is to determine if mucociliary clearance (MCC) dysfunction in idiopathic pulmonary
fibrosis (IPF) is due to abnormal multiciliated cell differentiation and function. Recent evidence suggests that IPF
may be a mucociliary disease caused by recurrent injury/inflammation/repair at the bronchoalveolar junction,
which is initiated and exacerbated by overexpression of MUC5B and reduced mucociliary function, retention of
particles, and enhanced lung injury.
 Motile cilia of multiciliated cells beat in a coordinated manner to propel inhaled contaminants trapped by the
mucus layer out of the lungs via MCC. Defects in airway clearance can precipitate and/or exacerbate acute
infections and chronic inflammatory conditions in pulmonary disease. In mice, our lab demonstrated that Muc5b
concentration in bronchoalveolar epithelia is related to impaired MCC and to the extent and persistence of
bleomycin-induced lung fibrosis, raising the question how disrupted motile cilia structure affects MCC and how
that leads to IPF. Even though ciliary abnormalities such as short, misaligned or ultrastructural cilia have been
reported in other pulmonary diseases, the origin of multiciliated cells, ciliary abnormalities, and its effect on MCC
dysfunction associated with MUC5B RNA and MUC5B protein in IPF has not been studied yet.
 My preliminary studies using wild-type mice have demonstrated that there are some regenerated motile cilia
with ciliary abnormalities upon airway damage. Further, association of MUC5B and cilia gene expression also
found in human IPF airway epithelial cells, providing a rationale for examining the role of multiciliated cells in this
disease. Thus, the aim of this proposal is to address the central hypothesis that MUC5B/Muc5b overexpression
in distal airway progenitor cells enhances ciliated cell fate acquisition, ciliary structural defects, and impaired
mucociliary clearance during repair following injury. This hypothesis will be tested in 3 Specific Aims: 1). Identify
the origin of multiciliated cells with cilia abnormalities and investigate their response in the bleomycin model of
lung fibrosis; 2). Test the hypothesis that mucociliary clearance dysfunction due to motile cilia abnormalities is
enhanced by Muc5b in the bleomycin lung fibrosis model.; 3). Determine the effect of the MUC5B promoter
variant on structure of motile cilia and mucociliary function of multiciliated cells in IPF lung.
 The proposed work will solve an existing challenge by defining the origin of multiciliated cells in the bleomycin
model and by identifying function of disrupted motile cilia of multiciliated cell, allowing to elucidate their role in
pathogenesis in IPF model. This work and the integrated training plan will allow the investigator to establish
comprehensive knowledge on lung injury and regeneration and expertise and skills to subsequently define the
molecular mechanism leading to successful lung tissue regene...

## Key facts

- **NIH application ID:** 10067682
- **Project number:** 1F32HL154666-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Eun Joo Kim
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $67,446
- **Award type:** 1
- **Project period:** 2021-01-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10067682

## Citation

> US National Institutes of Health, RePORTER application 10067682, The role of multiciliated cell dysfunction in pathogenesis of IPF (1F32HL154666-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10067682. Licensed CC0.

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