# Fibroblast Biology and Pulmonary Fibrosis

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2022 · $530,977

## Abstract

PROJECT SUMMARY
Idiopathic pulmonary fibrosis (IPF) is a disease characterized by progressive scarring of the lungs resulting in
deterioration in lung function with a median survival of 3.5 years. Pulmonary fibrosis is thought to be a disorder
of abnormal wound healing, wherein the initial trigger to the fibrotic response is injury to the alveolar
epithelium, followed by an exuberant, non-resolving wound-healing response. TGF-β is the key cytokine in the
pathogenesis of pulmonary fibrosis. TGF-β-driven differentiation of fibroblasts into myofibroblasts is a key
process in the pathogenesis of pulmonary fibrosis; however, the mechanisms of myofibroblast activation are
not completely understood.
In an unbiased approach using microarray studies, we identified Anoctamin-1 (ANO1), also known as
TMEM16A, as one of highly upregulated genes in response to TGF-β contributing to the proliferation, migration
and differentiation of lung fibroblasts to myofibroblasts. Our data also suggest that ANO1 is increased in the
lungs of IPF patients and is localized to the fibrotic areas in the IPF lung. The role of ANO1 in myofibroblast
activation and pulmonary fibrosis has been poorly investigated. Since ANO1 is a calcium-activated chloride
channel, we evaluated the role of chloride-sensitive protein kinase, With-No-Lysine Kinase-1 (WNK1), which
similarly to ANO1 contributed to myofibroblast activation. Based on our preliminary data, we hypothesize that
ANO1 is a pro-fibrotic protein promoting myofibroblast activation and pulmonary fibrosis through WNK1
pathway. To test our hypothesis, we propose the following specific aims:
Specific Aim #1. Determine how ANO1-mediated control of intracellular chloride levels activates human lung
fibroblasts (HLFs).
Specific Aim #2. Determine the signaling mechanisms of fibroblast activation through ANO1 and WNK1 in HLF.
Specific Aim #3. Elucidate the profibrotic role of ANO1 in the lung in vivo by a conditional knockout of ANO1 in
fibroblasts.

## Key facts

- **NIH application ID:** 10453449
- **Project number:** 5R01HL149993-03
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** NICKOLAI O DULIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $530,977
- **Award type:** 5
- **Project period:** 2020-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10453449

## Citation

> US National Institutes of Health, RePORTER application 10453449, Fibroblast Biology and Pulmonary Fibrosis (5R01HL149993-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10453449. Licensed CC0.

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