Targeting kidney resident macrophage niche filling to slow cystic kidney disease
Ended Project Grant Awarded Last action
- Award ID
- F31DK137568
- Recipient
-
University Of Oklahoma UEI GY8NMUZQXVS7
- Awarding agency
-
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $251,365
Award facts
- Assistance listing
- 93.847 Diabetes, Digestive, and Kidney Diseases Extramural Research
- Completion date
- Place of performance
- Oklahoma City, OK 73104, USA
Award details come from USAspending.gov.
Description
- Abstract
- Autosomal dominant polycystic kidney disease (adpkd) is the most commonly inherited kidney disease in the world. IT is characterized by large fluid-filled cysts that disrupt kidney function, eventually leading to end stage kidney disease. Previous literature indicates that kidney resident macrophages (KRM) are cyst-associated in human clinical samples and are also found in cystic regions of adpkd mouse models. KRM accelerate adpkd as depletion of KRM reduces cystic index and disease progression in mouse models of the disease. Together, these data suggest that targeting KRM may have a clinical impact in patients. Unfortunately, IT is currently not feasible to give patients macrophage depleting agents for long periods as these compounds lack specificity, depleting macrophage populations in multiple tissues. This is an important point as macrophages perform critical functions as part of an organism's innate immune defense. Additionally, adpkd progresses slowly and patients experience gradual cyst growth and loss of kidney function over several decades of life, thereby requiring long- term intervention. These data highlight that alternative approaches for long-term, kidney-specific resident macrophage depletion are desperately needed. In this application, i propose to study niche filling as a means to achieve long term, kidney specific resident macrophage depletion. This will be achieved by determining the mechanism of KRM niche filling after temporary depletion and through identification of factors, such as CX3CR1, that we propose are critical for KRM niche filling. The central hypothesis of this proposal is that following temporary depletion, the KRM niche is repopulated via the recruitment and differentiation of bone marrow- derived LY6CHI monocytes and that this process requires CX3CR1. In aim 1, i will map out the kinetics and mechanism of KRM niche after temporary depletion in a mouse model of adpkd. In aim 2, i will test if loss of CX3CR1 in monocytes is able to delay KRM niche filling and the progression of cystic disease. My long-term goal is to understand the mechanism of KRM niche filling and translationally apply KRM-centric findings to clinical cases of adpkd.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | -$10,556 | |
| Amendment | $564 | |
| Amendment | $564 | |
| Amendment | $37,439 | |
| Amendment | $37,439 | |
| Amendment | $37,439 | |
| Amendment | $1,280 | |
| Amendment | $1,280 | |
| Amendment | $1,280 | |
| Amendment | $36,159 | |
| Amendment | $36,159 | |
| Amendment | $36,159 | |
| Original award | $36,159 |
Show all 13
Quick answers
Who received award F31DK137568?
F31DK137568 was awarded to University Of Oklahoma by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) on September 28, 2024.
How much is award F31DK137568 worth?
$251,365 has been obligated on F31DK137568.
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award