# Pulmonary Fibrosis:  Novel Role for Developmental Gene Six1 in Alveolar Type II Cells

> **NIH NIH F30** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $25,567

## Abstract

Project Summary/Abstract
Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia with a median survival
time of 2-4 years after diagnosis. The alarming mortality rate is due to the lack of effective treatments. IPF is a
chronic, fibrotic disease that is characterized by alveolar destruction due to increasing extracellular matrix
deposition that leads to poor lung compliance, impaired gas exchange, and ultimately respiratory failure.
Repetitive alveolar epithelial injury is a central process to the underlying pathology with injury to the alveolar
stem-like cells, the type II alveolar epithelial cells (AECII) specifically, being a key player in the pathogenesis of
IPF. Recent studies have shown that recapitulation of developmental genes in alveolar epithelium, specifically
the AECII cells, is associated with the abnormal epithelial phenotype seen in IPF, however the mechanisms of
how they alter epithelial function are poorly understood. One such developmental gene that we show to be
inappropriately expressed in AECII in IPF is Sine Oculis Homeobox Homolog 1 (Six1), which is a transcription
factor that is essential for normal lung morphogenesis in utero. We have demonstrated increased expression of
Six1 in AECII isolated from patients with IPF. Furthemore, genetic deletion of Six1 in AECII using the
tamoxifen-inducible cre-lox system protected mice from the development of fibrosis. Taken together these
results point at an important role for Six1 in the development of fibrosis, yet the mechanisms are not fully
understood. Understanding the exact mechanisms by which Six1 acts on the AECII cells will be key to the
development of novel therapeutic targets and the advancement of the current scientific understanding of the
progression of pulmonary fibrosis. In this proposal we aim for the first time to identify the mechanisms whereby
Six1 modulates fibrosis.Thus, we propose to elaborate and evaluate these novel findings. We propose to
identify the molecular mechanisms by which Six1 acts on AECII cells and how this contributes to the
pathophysiology of pulmonary fibrosis with the hypothesis that increased Six1 expression in AECII cells
contributes to the development of pulmonary fibrosis. This comprehensive study of the function of Six1 will be
the first to characterize a role for Six1 in fibrosis. It will also provide the PI with substantial training and
experience to become a productive and innovative physician-scientist in the future.

## Key facts

- **NIH application ID:** 10022139
- **Project number:** 5F30HL147508-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Cory Wilson
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $25,567
- **Award type:** 5
- **Project period:** 2019-09-16 → 2021-06-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022139

## Citation

> US National Institutes of Health, RePORTER application 10022139, Pulmonary Fibrosis:  Novel Role for Developmental Gene Six1 in Alveolar Type II Cells (5F30HL147508-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10022139. Licensed CC0.

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