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Regulation of liver regeneration by hepatocyte-derived extracellular vesicles

Award Number: R01DK142985
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: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2030

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Regulation of liver regeneration by hepatocyte-derived extracellular vesicles - Abstract Text The liver exhibits a remarkable regenerative capacity following injury, a process predominantly mediated by hepatocyte proliferation. While cytokines and growth factors are known to play key roles in initiating and sustaining this response, the molecular mechanisms that regulate the precise timing of hepatocyte cell cycle entry and exit, thus governing the accurate restoration of liver mass, remain unknown. Emerging evidence suggests that microRNAs (miRNAs) play a key role in coordinating liver regeneration through precise post-transcriptional regulation of gene expression. Our recently published findings demonstrate that HD-EVs and their associated miRNAs contribute to a negative feedback mechanism that regulates hepatocyte proliferation during liver regeneration. Specifically, we identified miRNA-26a, miRNA-30a, and miRNA-33 as key regulators exhibiting inhibitory liver cell proliferation (ILCP) activity. This project aims to define the complete repertoire of ILCP-active miRNAs carried by HD-EVs, identify their mRNA targets and associated signaling pathways, and elucidate their mechanistic role in regulating liver regeneration. Using a rodent partial hepatectomy (PHx) model, we will (1) characterize EV populations and their dynamic changes during regeneration, (2) perform next-generation sequencing to profile miRNAs in HD-EVs and liver tissue, (3) validate ILCP activity in vitro and in vivo, and (4) construct and experimentally confirm miRNA/mRNA/pathway interaction networks. This comprehensive approach will provide new insights into the molecular regulation of liver regeneration and may uncover novel therapeutic targets for liver diseases characterized by regenerative dysfunction.


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 = $421,744 )
2026	2026	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/14/2026	NEW	$421,744
														Subtotal = $421,744

Grand Total All Awards = $421,744

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Regulation of liver regeneration by hepatocyte-derived extracellular vesicles

Award Number: R01DK142985

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: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2030

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