Page 43 - The Hormel Institute 2024 Annual Report

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Fibrosis is the thickening and scarring of tissue and represents the end-stage pathological outcome of numerous
chronic diseases, including idiopathic pulmonary fibrosis (IPF). A key characteristic of fibrosis is the accumulation of excess extracellular matrix components, which suggests that intrinsic mechanisms may be at play, enabling structural cells to activate the mesenchymal compartment by creating a fibrotic niche.
Healthy type 2 alveolar epithelial (AT2) cells are crucial for maintaining lung homeostasis. Their functions include secreting surfactant, trans- porting sodium and fluids, performing immuno- modulation, and serving as adult tissue stem cells involved in lung tissue maintenance, repair, and regeneration.
The overall goal of my team is to understand the role of AT2 cell plasticity in driving lung fibrosis, as well as the intrinsic and extrinsic mechanisms leading to AT2 cell failure. A greater understand- ing of these mechanisms could lead to better treatments and improved outcomes for patients.
In the past year, my team has been working on three projects:
1Our study has established a direct mech- anistic link between CEBPA repression, impaired AT2 cell identity, disrupted tissue
homeostasis, and lung fibrosis, which was recently published in the journal JCI Insight.
2We have identified S100A2 as a gene aberrantly expressed in IPF epithelial cells. This study aims to address the existing
knowledge gap by investigating the role of the IPF-associated target S100A2 in regulating AT2 cell identities and their profibrotic memory. Our research on this topic is currently ongoing.
3Understanding the role of the HIF pathway in lung fibrosis provides valuable insights into potential therapeutic targets. Inhib-
iting HIF or its downstream effectors offers a promising strategy to mitigate the pathological features of fibrosis and improve clinical outcomes for patients suffering from fibrotic lung diseases.
UMAP plots from single- cell RNA sequencing analysis of lung samples, illustrating disrupted tissue homeostasis in CebpaΔSftpc mutant murine strains compared to control strains.