Scholars@Duke
Kuo Du

Kuo Du

Assistant Professor in Medicine
Medicine, Gastroenterology

Selected Publications

Cellular senescence in liver diseases: From molecular drivers to therapeutic targeting.

Journal Article J Hepatol · January 2026 Obesity, metabolic syndrome, and aging are major contributors to the rising global burden of chronic liver diseases. Among these, aging remains an often underrecognised driver that intersects with other metabolic and environmental insults to exacerbate liv ... Full text Link to item Cite

Redefining senescence through hepatocyte fate changes in liver diseases.

Journal Article Trends Endocrinol Metab · August 28, 2025 Hepatocyte senescence is increasingly recognized as a key contributor to liver pathophysiology. While traditionally viewed as a state of permanent growth arrest, hepatocyte senescence is now understood to be more dynamic and potentially reversible, particu ... Full text Link to item Cite

WSTF nuclear autophagy regulates chronic but not acute inflammation.

Journal Article Nature · August 2025 Acute inflammation is an essential response that our bodies use to combat infections1. However, in the absence of infections, chronic inflammation can have a pivotal role in the onset and progression of chronic diseases, such as arthritis, cancer, autoimmu ... Full text Open Access Link to item Cite

Targeting senescent hepatocytes for treatment of metabolic dysfunction-associated steatotic liver disease and multi-organ dysfunction.

Journal Article Nat Commun · March 28, 2025 Senescent hepatocytes accumulate in metabolic dysfunction-associated steatotic liver disease (MASLD) and are linked to worse clinical outcomes. However, their heterogeneity and lack of specific markers have made them difficult to target therapeutically. He ... Full text Link to item Cite

A systemic effect for liver senescence.

Journal Article Nat Cell Biol · December 2024 A study reveals that senescence induced in the liver can spread systemically to precipitate multi-organ dysfunction. The work identifies TGFβ signaling as a key mediator of this transmission, suggesting therapeutic avenues to prevent multi-organ failure in ... Full text Link to item Cite

The senescence-associated secretome of Hedgehog-deficient hepatocytes drives MASLD progression.

Journal Article J Clin Invest · August 27, 2024 The burden of senescent hepatocytes correlates with the severity of metabolic dysfunction-associated steatotic liver disease (MASLD), but the mechanisms driving senescence and how it exacerbates MASLD are poorly understood. Hepatocytes experience lipotoxic ... Full text Link to item Cite

Aging promotes metabolic dysfunction-associated steatotic liver disease by inducing ferroptotic stress.

Journal Article Nat Aging · July 2024 Susceptibility to the biological consequences of aging varies among organs and individuals. We analyzed hepatocyte transcriptomes of healthy young and aged male mice to generate an aging hepatocyte gene signature, used it to deconvolute transcriptomic data ... Full text Link to item Cite

Plasticity, heterogeneity, and multifunctionality of hepatic stellate cells in liver pathophysiology.

Journal Article Hepatol Commun · May 1, 2024 HSCs, the resident pericytes of the liver, have consistently been at the forefront of liver research due to their crucial roles in various hepatic pathological processes. Prior literature often depicted HSCs in a binary framework, categorizing them as eith ... Full text Link to item Cite

Hedgehog Signaling: Implications in Liver Pathophysiology.

Journal Article Semin Liver Dis · November 2023 The purpose of this review is to summarize current knowledge about the role of the Hedgehog signaling pathway in liver homeostasis and disease. Hedgehog is a morphogenic signaling pathway that is active in development. In most healthy tissues, pathway acti ... Full text Link to item Cite

Targeting senescent hepatocytes using the thrombomodulin-PAR1 inhibitor vorapaxar ameliorates NAFLD progression.

Journal Article Hepatology · October 1, 2023 BACKGROUND AND AIMS: Senescent hepatocytes accumulate in parallel with fibrosis progression during NASH. The mechanisms that enable progressive expansion of nonreplicating cell populations and the significance of that process in determining NASH outcomes a ... Full text Open Access Link to item Cite

Antagonizing the irreversible thrombomodulin-initiated proteolytic signaling alleviates age-related liver fibrosis via senescent cell killing.

Journal Article Cell Res · July 2023 Cellular senescence is a stress-induced, stable cell cycle arrest phenotype which generates a pro-inflammatory microenvironment, leading to chronic inflammation and age-associated diseases. Determining the fundamental molecular pathways driving senescence ... Full text Open Access Link to item Cite

Targeting YAP-mediated HSC death susceptibility and senescence for treatment of liver fibrosis.

Conference Hepatology · June 1, 2023 BACKGROUND AND AIMS: Liver fibrosis results from the accumulation of myofibroblasts (MFs) derived from quiescent HSCs, and yes-associated protein (YAP) controls this state transition. Although fibrosis is also influenced by HSC death and senescence, whethe ... Full text Open Access Link to item Cite

Hepatocyte Smoothened Activity Controls Susceptibility to Insulin Resistance and Nonalcoholic Fatty Liver Disease.

Conference Cell Mol Gastroenterol Hepatol · 2023 BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH), a leading cause of cirrhosis, strongly associates with the metabolic syndrome, an insulin-resistant proinflammatory state that disrupts energy balance and promotes progressive liver degeneration. We a ... Full text Link to item Cite

Aging reduces liver resiliency by dysregulating Hedgehog signaling.

Conference Aging Cell · February 2022 Older age is a major risk factor for damage to many tissues, including liver. Aging undermines resiliency and impairs liver regeneration. The mechanisms whereby aging reduces resiliency are poorly understood. Hedgehog is a signaling pathway with critical m ... Full text Link to item Cite

Inhibiting xCT/SLC7A11 induces ferroptosis of myofibroblastic hepatic stellate cells but exacerbates chronic liver injury.

Journal Article Liver Int · September 2021 BACKGROUND & AIMS: The outcome of liver injury is dictated by factors that control the accumulation of myofibroblastic (activated) hepatic stellate cells (MF-HSCs) but therapies that specifically block this process have not been discovered. We evaluated th ... Full text Link to item Cite

Mitochondrial protein adduct and superoxide generation are prerequisites for early activation of c-jun N-terminal kinase within the cytosol after an acetaminophen overdose in mice.

Journal Article Toxicol Lett · March 1, 2021 Acetaminophen (APAP) overdose is the most common cause of acute liver failure in the United States and formation of APAP-protein adducts, mitochondrial oxidant stress and activation of the mitogen activated protein (MAP) kinase c-jun N-terminal kinase (JNK ... Full text Link to item Cite

Succinate-GPR-91 receptor signalling is responsible for nonalcoholic steatohepatitis-associated fibrosis: Effects of DHA supplementation.

Journal Article Liver Int · April 2020 BACKGROUND AND AIMS: Treatment of non-alcoholic steatohepatitis (NASH) is challenging, because suppressing fibrotic progression has not been achieved consistently by drug candidates currently in clinical trials. The aim of this study was to investigate the ... Full text Link to item Cite

Epithelial splicing regulatory protein 2-mediated alternative splicing reprograms hepatocytes in severe alcoholic hepatitis.

Journal Article J Clin Invest · April 1, 2020 Severe alcoholic hepatitis (SAH) is a deadly liver disease without an effective medical therapy. Although SAH mortality is known to correlate with hepatic accumulation of immature liver cells, why this occurs and how it causes death are unclear. Here, we d ... Full text Link to item Cite

Increased Glutaminolysis Marks Active Scarring in Nonalcoholic Steatohepatitis Progression.

Journal Article Cell Mol Gastroenterol Hepatol · 2020 BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) occurs in the context of aberrant metabolism. Glutaminolysis is required for metabolic reprograming of hepatic stellate cells (HSCs) and liver fibrogenesis in mice. However, it is unclear how changes i ... Full text Open Access Link to item Cite

Single-Cell RNA Sequencing Identifies Yes-Associated Protein 1-Dependent Hepatic Mesothelial Progenitors in Fibrolamellar Carcinoma.

Journal Article Am J Pathol · January 2020 Fibrolamellar carcinoma (FLC) is characterized by in-frame fusion of DnaJ heat shock protein family (Hsp40) member B1 (DNAJB1) with protein kinase cAMP-activated catalytic subunit α (PRKACA) and by dense desmoplasia. Surgery is the only effective treatment ... Full text Link to item Cite

Mito-tempo protects against acute liver injury but induces limited secondary apoptosis during the late phase of acetaminophen hepatotoxicity.

Journal Article Arch Toxicol · January 2019 We previously reported that delayed treatment with Mito-tempo (MT), a mitochondria-targeted superoxide dismutase mimetic, protects against the early phase of acetaminophen (APAP) hepatotoxicity by inhibiting peroxynitrite formation. However, whether this p ... Full text Link to item Cite

Hedgehog-YAP Signaling Pathway Regulates Glutaminolysis to Control Activation of Hepatic Stellate Cells.

Conference Gastroenterology · April 2018 BACKGROUND & AIMS: Cirrhosis results from accumulation of myofibroblasts derived from quiescent hepatic stellate cells (Q-HSCs); it regresses when myofibroblastic HSCs are depleted. Hedgehog signaling promotes transdifferentiation of HSCs by activating Yes ... Full text Link to item Cite

Induction of mitochondrial biogenesis protects against acetaminophen hepatotoxicity.

Journal Article Food Chem Toxicol · October 2017 Mitochondrial biogenesis (MB) is an adaptive response to maintain metabolic homeostasis after mitochondrial dysfunction. Induction of MB during APAP hepatotoxicity has not been studied. To investigate this, mice were treated with toxic doses of APAP and eu ... Full text Link to item Cite

Dual Role of Epidermal Growth Factor Receptor in Liver Injury and Regeneration after Acetaminophen Overdose in Mice.

Journal Article Toxicol Sci · February 2017 Epidermal growth factor receptor (EGFR) plays a crucial role in hepatocyte proliferation. Its role in acetaminophen (APAP)-mediated hepatotoxicity and subsequent liver regeneration is completely unknown. Role of EGFR after APAP-overdose in mice was studied ... Full text Link to item Cite

Mitochondria-targeted antioxidant Mito-Tempo protects against acetaminophen hepatotoxicity.

Journal Article Arch Toxicol · February 2017 Acetaminophen (APAP) hepatotoxicity is characterized by an extensive mitochondrial oxidant stress. However, its importance as a drug target has not been clarified. To investigate this, fasted C57BL/6J mice were treated with 300 mg/kg APAP and the mitochond ... Full text Link to item Cite

Differential susceptibility to acetaminophen-induced liver injury in sub-strains of C57BL/6 mice: 6N versus 6J.

Journal Article Food Chem Toxicol · December 2016 UNLABELLED: Mouse models of acetaminophen (APAP) hepatotoxicity are considered relevant for the human pathophysiology. The C57BL/6 strain is most popular because it is the background strain of gene knock-out mice. However, conflicting results in the litera ... Full text Link to item Cite

Editor's Highlight: Metformin Protects Against Acetaminophen Hepatotoxicity by Attenuation of Mitochondrial Oxidant Stress and Dysfunction.

Journal Article Toxicol Sci · December 2016 Overdose of acetaminophen (APAP) causes severe liver injury and even acute liver failure in both mice and human. A recent study by Kim et al. (2015, Metformin ameliorates acetaminophen hepatotoxicity via Gadd45β-dependent regulation of JNK signaling in mic ... Full text Link to item Cite

Oxidative stress during acetaminophen hepatotoxicity: Sources, pathophysiological role and therapeutic potential.

Journal Article Redox Biol · December 2016 Acetaminophen (APAP) hepatotoxicity is characterized by an extensive oxidative stress. However, its source, pathophysiological role and possible therapeutic potential if targeted, have been controversially described. Earlier studies argued for cytochrome P ... Full text Open Access Link to item Cite

Removal of acetaminophen protein adducts by autophagy protects against acetaminophen-induced liver injury in mice.

Journal Article J Hepatol · August 2016 BACKGROUND & AIMS: Acetaminophen (APAP)-induced liver injury is the most frequent cause of acute liver failure in the US and many other countries. Metabolism of APAP results in formation of APAP protein adducts (APAP-AD) in hepatocytes and triggers mitocho ... Full text Link to item Cite

Liuweiwuling tablets protect against acetaminophen hepatotoxicity: What is the protective mechanism?

Journal Article World J Gastroenterol · March 21, 2016 Study of the effects of natural products, including traditional Chinese Medicines, on acetaminophen hepatotoxicity has gained considerable popularity in recent years, and some of them showed positive results and even promising therapeutic potentials. A rec ... Full text Link to item Cite

Critical review of resveratrol in xenobiotic-induced hepatotoxicity.

Journal Article Food Chem Toxicol · December 2015 Use of natural products is increasingly popular. In fact, many patients with liver diseases self-medicate with herbal supplements. Resveratrol (RSV), in particular, is a common natural product that can reduce injury in experimental models of liver disease. ... Full text Link to item Cite

Mitochondrial protein adducts formation and mitochondrial dysfunction during N-acetyl-m-aminophenol (AMAP)-induced hepatotoxicity in primary human hepatocytes.

Journal Article Toxicol Appl Pharmacol · December 1, 2015 3'-Hydroxyacetanilide orN-acetyl-meta-aminophenol (AMAP) is generally regarded as a non-hepatotoxic analog of acetaminophen (APAP). Previous studies demonstrated the absence of toxicity after AMAP in mice, hamsters, primary mouse hepatocytes and several ce ... Full text Link to item Cite

Benzyl alcohol protects against acetaminophen hepatotoxicity by inhibiting cytochrome P450 enzymes but causes mitochondrial dysfunction and cell death at higher doses.

Journal Article Food Chem Toxicol · December 2015 Acetaminophen (APAP) hepatotoxicity is a serious public health problem in western countries. Current treatment options for APAP poisoning are limited and novel therapeutic intervention strategies are needed. A recent publication suggested that benzyl alcoh ... Full text Link to item Cite

Resveratrol prevents protein nitration and release of endonucleases from mitochondria during acetaminophen hepatotoxicity.

Journal Article Food Chem Toxicol · July 2015 Overdose of acetaminophen (APAP) is a common cause of acute liver injury and liver failure. The mechanism involves formation of a reactive metabolite, protein binding, oxidative stress and activation of c-Jun N-terminal kinase (JNK), mitochondrial dysfunct ... Full text Link to item Cite

The role of the c-Jun N-terminal kinases 1/2 and receptor-interacting protein kinase 3 in furosemide-induced liver injury.

Journal Article Xenobiotica · May 2015 1. The mechanisms of furosemide (FS) hepatotoxicity were explored in mice. Specifically, C57Bl/6 J mice were treated with 500 mg FS/kg bodyweight, and c-Jun N-terminal kinase (JNK) activation and receptor-interacting protein kinase 3 (RIP3) expression were ... Full text Link to item Cite

Pathophysiological significance of c-jun N-terminal kinase in acetaminophen hepatotoxicity.

Journal Article Expert Opin Drug Metab Toxicol · 2015 BACKGROUND: Acetaminophen (APAP) overdose is the leading cause of acute liver failure in the US. Although substantial progress regarding the mechanisms of APAP hepatotoxicity has been made in the past several decades, therapeutic options are still limited ... Full text Link to item Cite

Lower susceptibility of female mice to acetaminophen hepatotoxicity: Role of mitochondrial glutathione, oxidant stress and c-jun N-terminal kinase.

Journal Article Toxicol Appl Pharmacol · November 15, 2014 UNLABELLED: Acetaminophen (APAP) overdose causes severe hepatotoxicity in animals and humans. However, the mechanisms underlying the gender differences in susceptibility to APAP overdose in mice have not been clarified. In our study, APAP (300mg/kg) caused ... Full text Link to item Cite

The gap junction inhibitor 2-aminoethoxy-diphenyl-borate protects against acetaminophen hepatotoxicity by inhibiting cytochrome P450 enzymes and c-jun N-terminal kinase activation.

Journal Article Toxicol Appl Pharmacol · December 15, 2013 Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the US. Although many aspects of the mechanism are known, recent publications suggest that gap junctions composed of connexin32 function as critical intercellular communicat ... Full text Link to item Cite

Critical role of FoxO3a in alcohol-induced autophagy and hepatotoxicity.

Journal Article Am J Pathol · December 2013 Autophagy is a lysosomal degradation process that degrades long-lived cellular proteins and damaged organelles as a critical cell survival mechanism in response to stress. We recently reported that acute ethanol induces autophagy, which then reduces ethano ... Full text Link to item Cite