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Renal medullary telocyte in pressure natriuresis and arterial blood pressure control: Piezo1 channel as a pressure sensor

Award Number: R01DK149540
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: 08/13/2026
PERIOD OF PERFORMANCE END DATE: 03/31/2030

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Renal medullary telocyte in pressure natriuresis and arterial blood pressure control: Piezo1 channel as a pressure sensor - Project Summary Long-term regulation of arterial blood pressure (BP) critically depends on renal mechanisms that respond to changes in renal perfusion pressure (RPP). Pressure natriuresis, a process by which elevated RPP promotes sodium excretion, is central to this regulation. The renal medulla is key to this process, but the molecular sensors and signaling pathways involved remain unclear. Emerging evidence suggests that exosome release from renal medullary cells may contribute to BP regulation, yet the upstream mechanosensory mechanisms are unknown. Piezo1 is a mechanosensitive ion channel activated by mechanical forces such as hydrostatic pressure. It facilitates calcium influx and initiates downstream signaling cascades. Telocytes - interstitial cells enriched in the renal medulla express Piezo1 and are capable of releasing exosomes, positioning them as potential mechanosensory regulators of pressure natriuresis. Preliminary data from a telocyte-specific Piezo1 knockout (Piezo1fl/fl/Telocre) mouse model reveal impaired natriuresis, reduced circulating exosome levels, and exacerbated salt-sensitive hypertension, supporting a functional role for Piezo1 in BP regulation. This grant proposal aims to elucidate the role of Piezo1 channels in renal medullary telocytes as mechanosensors that regulate BP via exosome-mediated signaling. Specific Aim 1 will determine the role of renomedullary telocyte Piezo1 channels in BP regulation by assessing the impact of telocyte-specific Piezo1 gene KO on pressure natriuresis and salt-sensitive hypertension in Piezo1fl/fl/Telocre mice. Specific Aim 2 will characterize the mechanosensitive properties of Piezo1 channels in telocytes by investigating the relationship between mechanical stimulation, Piezo1 activation, Ca2+ influx, and exosome release in cultured renomedullary telocytes. Specific Aim 3 will elucidate the molecular mechanisms by which renal medullary telocytes regulate BP with a focus on the role of Piezo1-dependent exosome release from telocytes in mediating antihypertensive responses to increased RPP. The findings will define a novel mechanosensory pathway in the renal medulla and uncover telocyte Piezo1 channels as critical regulators of BP homeostasis.


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 = $714,743 )
2026	2026	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/13/2026	NEW	$714,743
														Subtotal = $714,743

Grand Total All Awards = $714,743

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Renal medullary telocyte in pressure natriuresis and arterial blood pressure control: Piezo1 channel as a pressure sensor

Award Number: R01DK149540

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: 08/13/2026

PERIOD OF PERFORMANCE END DATE: 03/31/2030

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