The role of pleural mesothelium in lung injury, repair, and regeneration
Active Project Grant Awarded Last action
- Award ID
- F32HL175907
- Recipient
-
Mayo Clinic UEI Y2K4F9RPRRG7 Part of Mayo Clinic
- Awarding agency
-
National Heart Lung and Blood Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $314,188
Award facts
- Assistance listing
- 93.837 Cardiovascular Diseases Research
- Completion date 73% complete
- Place of performance
- Rochester, MN 55905, USA
Award details come from USAspending.gov.
Description
- Abstract
- The mechanisms involved in lung repair and regeneration are still poorly understood and currently no clinical techniques are available to specifically induce lung repair. In young tissues, the lung is appreciated to repair and regenerate in response to damage. However, lung diseases such as idiopathic pulmonary fibrosis, are largely considered diseases of aging and subsequent disordered repair. Current treatment options available are limited, and mainly provide an option to slow disease progression, but none offer the ability to repair existing damage. Improved understanding of repair and regenerative mechanisms could drastically improve the treatment options available for these terminal fibrotic conditions. Of the cells studied in repair and regeneration, mesothelial cells are largely excluded, presenting a GAP in the knowledge base. While pleural mesothelial cells (pmcs) are largely quiescent in healthy conditions, our preliminary data shows recruitment and migration of pmcs in a mouse model of transient fibrotic injury. Compelling data also exists for PMC recruitment and migration in a mouse model of lung regeneration. Contradicting this, other work has suggested that pmcs serve a role to stimulate fibrotic progression, leading to confusion surrounding the function of these cells. The lack of study and contradictory evidence regarding PMC functions in lung injury, fibrosis and repair sets the stage for detailed study of this cell population and the signaling and functional roles IT may play in these contexts. Using a combination of careful lineage-tracing experiments, we will investigate pmcs in the bleomycin injury model, as well as in the pneumonectomy compensatory growth and regeneration model. We will subsequently collect these cells for further genomic analysis to assess expression of genes consistent with injury progression or controlled repair. Our initial investigations into the signaling of pmcs has capitalized on the various lung single-cell RNA sequencing dataset that are publically available. In multiple human and mouse datasets, the cell clusters identified as mesothelium represent the exclusive lung cell type that expresses the WNT mediator r-spondin 1 (RSPO1). Our preliminary data confirms PMC to be highly expressive of RSPO1. As WNT signaling is a pathway that has been well explored in contexts of injury and repair, this proposal will explore the ability of pmcs to modulate WNT signaling in the local environment but using organoid CO-culture. The goal of these studies is to provide context for the effect of these cells on specific cell types involved in lung injury and repair. Overall, the studies may reveal a unique and unexplored potential to target pleural mesothelial cells and explore their expanded role in lung function/dysfunction.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $84,580 | |
| Amendment | $81,040 | |
| Amendment | $0 | |
| Amendment | $74,284 | |
| Amendment | $74,284 | |
| Original award | $0 |
Quick answers
Who received award F32HL175907?
F32HL175907 was awarded to Mayo Clinic by National Heart Lung and Blood Institute (National Institutes of Health) on December 25, 2024.
How much is award F32HL175907 worth?
$314,188 has been obligated on F32HL175907.
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