Disrupting Six/Eya Signalling as New Therapy for Lung Fibrosis
Abstract
Pulmonary fibrosis is frequently encountered in the United States Veteran population. Among the different types of pulmonary fibrosis, Idiopathic pulmonary fibrosis (IPF) remains a disease with a dire prognosis with patients progressing to respiratory failure and death within a few years of diagnosis. Unfortunately, limited curative options are available, and prognosis remains extremely poor. This research proposal aims to evaluate the capacity of pharmacological and gene therapy aimed at a novel molecular target for lung fibrosis. This proposal is highly relevant to the FY18 PRMRP Pulmonary Fibrosis and Respiratory Health Topic Areas. IPF is a lethal lung disease that affects about 200,000 people in the United States. Studies have shown that most patients die within 5 years after diagnosis. Despite its prevalence, the pathogenesis of pulmonary fibrosis is poorly understood due to a lack of knowledge of the mechanisms governing its progression. Evidence suggests that pulmonary fibrosis results from aberrant repair responses in the damaged lung. Thus, there is a critical need to identify the mechanisms that lead to overactive repair processes contributing to the development of fibrosis in order to develop new therapies to interrupt the progression of disease and reduce mortality. Sine Oculis Homeobox Homolog 1 (Six1) is a transcription factor that is essential for normal lung morphogenesis in utero and is expressed in both mice and humans. The Six family encompasses Six1-6, all of them are expressed in mice and humans. Studies have shown that Six1 is important in the development of the lung where its absence results in lung hypoplasia. In these experiments Six1 was shown to modulate expression of the developmental genes sonic hedgehog (SHH) and the epithelial cell markers surfactant protein B and C.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2021
- Accession Number
- AD1158233
Entities
People
- Harry Karmouty-Quintana
Organizations
- University of Texas Health Science Center at Houston