Targeting mash/fibrosis: critical regulation by kisspeptin signaling

Active Project Grant Awarded Last action

Award ID
F31DK149482
Recipient
Awarding agency
Obligated
$43,714

Award facts

Assistance listing
93.847 Diabetes, Digestive, and Kidney Diseases Extramural Research
Completion date 0% complete
Place of performance
Newark, NJ 07107, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Metabolic dysfunction-associated steatotic liver disease (masld), formerly referred to as nonalcoholic fatty liver disease (nafld), is now the most common chronic liver disease worldwide and a leading cause of cirrhosis, liver failure, and transplantation. Although fibrosis is the strongest predictor of morbidity and mortality, there are no FDA-approved therapies that directly target fibrosis, highlighting a critical unmet need. Hepatic fibrosis results from excessive extracellular matrix deposition driven by activated hepatic stellate cells (hscs). Our recent work identified the kisspeptin receptor (KISS1R) as a previously unrecognized protective pathway in masld; enhancing KISS1R signaling improves hepatic steatosis, reduces inflammation, and fibrosis in mouse models, and suppresses fibrogenic and inflammatory signaling in human precision-cut liver sections (from patient fibrotic liver sections). However, the underlying mechanisms by which KISS1R signaling regulates inflammation and fibrosis remain largely unknown. Our new preliminary studies have identified that KISS1R downregulates thioredoxin-interacting protein (txnip), a key mediator of oxidative stress, inflammasome activation, and HSC activation whose expression increases with fibrosis severity in humans. The goal of this project is to define how KISS1R signaling in hepatocytes and hscs regulates txnip-dependent metabolic and inflammatory pathways during masld progression. Aim 1 will test whether cell-specific KISS1R overexpression attenuates steatohepatitis and fibrosis in vivo and aim 2 will determine how KP/KISS1R signaling suppresses txnip mechanistically. Completion of this project will establish the KISS1R as a novel antifibrotic pathway and support development of new therapeutic strategies for masld. This F31 will provide rigorous training in liver biology, metabolomics, transcriptomics, gene manipulation, for a career in translational research.

Quick answers

Who received award F31DK149482?

F31DK149482 was awarded to Rutgers The State University Of New Jersey by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) on May 1, 2027.

How much is award F31DK149482 worth?

$43,714 has been obligated on F31DK149482.

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