Wednesday, July 2, 2025 7/2/2025

Role of PON3 in regulating renal Na+ and K+ homeostasis

Award Number: R01DK130901
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: 09/15/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2026

Group Awards By:

View Award Description

Role of PON3 in regulating renal Na+ and K+ homeostasis - ABSTRACT The mammalian paraoxonase (PON) family consists of three highly conserved members (PON1, PON2 and PON3) with unique anti-oxidative and anti-atherosclerotic properties. PON1 and 2 have been implicated in blood pressure (BP) regulation. While the role of PON3 in regulating BP has not been investigated, it is expressed in the aldosterone-sensitive distal nephron where the fine tuning of Na+ absorption and K+ secretion occurs. PONs share key structural and functional features with MEC-6, an endoplasmic reticulum-resident chaperone of C. elegans. MEC-6 is required for proper folding, assembly, and surface expression of the mechanosensitive degenerin channel in touch receptor neurons. The chaperon function is conserved between mammalian PONs and C. elegans MEC-6. We have previously shown that both PON2 and PON3 regulate functional expression of the epithelial Na+ channel (ENaC), a member of the ENaC/degenerin family of ion channels. ENaC mediates the rate-limiting step of Na+ reabsorption in distal nephron and has a key role in volume and BP control. While the constitutive K+ secretion is conducted by the renal outer medullary K+ (ROMK) channels, ENaC-dependent and flow-induced K+ secretion is mediated by the large conductance K+ (BK) channels. In the preliminary studies, we found that Pon3 KO mice have higher ENaC activity and enhanced amiloride-sensitive natriuresis, suggesting ENaC functional expression is upregulated in the absence of PON3. In addition, we have identified BK channel as a novel target of PON3. When expressed in HEK293 cells, PON3 interacted with BK α subunit to reduce its surface expression and channel activity. Our proposed studies will define mechanisms by which PON3 functions as a chaperone in the regulation of ENaC and BK expression. We will determine the consequences of deleting PON3 in renal Na+ and K+ handling and BP control in mice. Successful completion our proposed studies will enhance our understanding of the mechanisms by which PONs function as chaperones and their physiological roles in kidney function and BP control.


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: 2024 ( Subtotal = $305,280 )
2024	2024	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	7/25/2024	NON-COMPETING CONTINUATION	$305,280
														Subtotal = $305,280

Issue Date FY: 2023 ( Subtotal = $318,000 )
2023	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	8/24/2023	NON-COMPETING CONTINUATION	$318,000
														Subtotal = $318,000

Issue Date FY: 2022 ( Subtotal = $318,000 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	8/30/2022	NON-COMPETING CONTINUATION	$318,000
2022	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/30/2022	NEW	$0
														Subtotal = $318,000

Issue Date FY: 2021 ( Subtotal = $313,000 )
2021	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/15/2021	NEW	$313,000
														Subtotal = $313,000

Grand Total All Awards = $1,254,280

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Role of PON3 in regulating renal Na+ and K+ homeostasis

Award Number: R01DK130901

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: 09/15/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer