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Novel mechanism of activation of the Renin-Angiotensin-System by inflammatory cells in diabetic kidney disease

Award Number: R21DK138393
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/25/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2025

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Novel mechanism of activation of the Renin-Angiotensin-System by inflammatory cells in diabetic kidney disease - PROJECT ABSTRACT There is a critical need to identify new mechanisms and signaling pathways promoting diabetic kidney disease. Intrarenal expression of renin and pro-renin are enhanced in diabetes and blockade of the renin angiotensin system improves diabetic kidney disease (DKD) and kidney function. Pro-renin is elevated in plasma of patients and mice with type-1 diabetes and plays a role in DKD, independently from its role in blood pressure. The main source of the circulating renin and pro-renin are Juxtaglomerular Cells (JG cells) located in the afferent arteriole. Pro-inflammatory cells infiltrate the diabetic kidney cortex, increasing the release of interleukins (IL). The specific inflammatory cells and their localization in the cortex in diabetic mice is not clear. Our preliminary data shows an increased number of T lymphocytes (Th17) in kidneys from diabetic mice. Our data also show that IL17 increases renin release from JG cells and that receptors for IL17 (IL17-R) are enhanced in JG cells from diabetic mice suggesting that this pathway could be in volved in activation of the kidney renin angiotensin system in diabetes. In this exploratory grant we will identify new subpopulations of inflammatory cells in the renal cortex of diabetic mice by single cell RNA seq and mass cytometry and study their localization in the juxtaglomerular area by CyToF imaging. In addition, we will develop a triple transgenic diabetic mouse with specific deletion of IL17R in JG cells to determine the role of this pathway in DKD.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$76,424 )
2026	2025	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	11/19/2025	NON-COMPETING CONTINUATION	-$76,424
														Subtotal = -$76,424

Issue Date FY: 2025 ( Subtotal = $173,250 )
2025	2025	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	5/1/2025	NON-COMPETING CONTINUATION	$0
2025	2025	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	1/22/2025	NON-COMPETING CONTINUATION	$173,250
														Subtotal = $173,250

Issue Date FY: 2024 ( Subtotal = $192,500 )
2024	2024	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	1/19/2024	NEW	$192,500
														Subtotal = $192,500

Grand Total All Awards = $289,326

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Novel mechanism of activation of the Renin-Angiotensin-System by inflammatory cells in diabetic kidney disease

Award Number: R21DK138393

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/25/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2025

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