Insight into the function of the Golgi membrane protein GOLM1 in cholangiocytes through interactomic analysis DOI Open Access
Meghana Nagaraj, Emmagouni Sharath Kumar Goud, Vaishali Chaurasiya

et al.

FEBS Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

GOLM1, a Golgi membrane protein, is upregulated in cancers and liver diseases. Analysis of public RNAseq data from healthy human suggested that GOLM1 predominantly expressed cholangiocytes. Therefore, this study was initiated to understand the molecular functions cholangiocytes through protein interactomics. The findings reveal number putative GOLM1-interacting partners involved cellular regimes such as mitochondrial functions, ribonucleoprotein biogenesis, cell cycle, basement organization. Further, validate select key roles, silenced MMNK-1 effects on were studied. silencing resulted impaired function, reduced P-body markers, increased apoptosis, adhesion, suggesting crucial roles maintaining normal cholangiocyte metabolism function.

Language: Английский

Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH) DOI
Shuang Wang, Scott L. Friedman

Science Translational Medicine, Journal Year: 2023, Volume and Issue: 15(716)

Published: Oct. 4, 2023

Metabolic dysfunction–associated steatohepatitis (MASH) is a severe form of liver disease that poses global health threat because its potential to progress advanced fibrosis, leading cirrhosis and cancer. Recent advances in single-cell methodologies, refined models, genetic epigenetic insights have provided nuanced understanding MASH fibrogenesis, with substantial cellular heterogeneity livers providing potentially targetable cell-cell interactions behavior. Unlike mechanisms underlying fibrosis regression are still inadequately understood, although antifibrotic targets been recently identified. A treatment framework could lead noninvasive assessment targeted therapies preserve hepatocellular function restore the liver’s architectural integrity.

Language: Английский

Citations

60
Spatially restricted and ontogenically distinct hepatic macrophages are required for tissue repair DOI Creative Commons
Federico F. De Ponti, Anna Bujko, Zhuangzhuang Liu

et al.

Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Our understanding of the functional heterogeneity resident versus recruited macrophages in diseased liver is limited. A population lipid-associated (LAMs) has been reported to populate alongside Kupffer cells (KCs). However, precise roles these distinct macrophage subsets remain elusive. Here, using proteogenomics, we have identified LAMs multiple models injury. Moreover, found that this phenotype not specific macrophages, as a subset KCs can also adopt LAM-like mouse and human liver. By combining genetic targeting populations, determined both play crucial tissue repair. Specifically, triggering receptor expressed on myeloid 2 (TREM2) expression either or required for efficient clearance dying cells, enhancing repair preventing exacerbated fibrosis.

Language: Английский

Citations

6
Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics DOI Creative Commons
Xiao Ma, Tengda Huang, Xi Chen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 8, 2025

Language: Английский

Citations

5
Hepatic stellate cells control liver zonation, size and functions via R-spondin 3 DOI Creative Commons
Atsushi Sugimoto, Yoshinobu Saito,

Guanxiong Wang

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

Abstract Hepatic stellate cells (HSCs) have a central pathogenetic role in the development of liver fibrosis. However, their fibrosis-independent and homeostatic functions remain poorly understood 1–5 . Here we demonstrate that genetic depletion HSCs changes WNT activity zonation hepatocytes, leading to marked alterations regeneration, cytochrome P450 metabolism injury. We identify R-spondin 3 (RSPO3), an HSC-enriched modulator signalling, as responsible for these hepatocyte-regulatory effects HSCs. HSC-selective deletion Rspo3 phenocopies HSC on hepatocyte gene expression, zonation, size, regeneration P450-mediated detoxification, exacerbates alcohol-associated metabolic dysfunction-associated steatotic disease. RSPO3 expression decreases with activation is inversely associated outcomes patients These protective hepatocyte-regulating via resemble R-spondin-expressing stromal niche other organs should be integrated into current therapeutic concepts.

Language: Английский

Citations

2
Update on the management of acute liver failure DOI
Ole Andreas Nilsen, Caleb Fisher, Stephen Warrillow

et al.

Current Opinion in Critical Care, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Purpose of review Acute liver failure (ALF) is a rare, life-threatening but potentially reversible clinical syndrome characterized by multiple organ secondary to the rapid loss function. Key management challenges include severe cerebral oedema and complex treatments support failure. This focuses on fundamental principles recent treatment advances. Recent findings Identifying cause ALF key guiding specific therapies. The early commencement continuous renal replacement therapy (CRRT) control hyperammonaemia can now be considered an important standard care, plasma exchange may have role in sickest patients; however, other blood purification modalities still lack supporting evidence. Close monitoring, regular investigations, careful attention neuroprotective measures, as well optimizing general physiological supports essential. Where possible, patients should transferred transplant centre achieve best chance transplant-free survival, or undergo emergency transplantation if required. Summary outlines current management, emerging strategies, practical approach ICU. These recommendations form development local guidelines, incorporating evidence for managing this rare often lethal condition.

Language: Английский

Citations

1
Characteristic immune cell interactions in livers of children with acute hepatitis revealed by spatial single-cell analysis identify a possible postacute sequel of COVID-19 DOI

Felix Röttele,

A Zollner, Carolin Mogler

et al.

Gut, Journal Year: 2025, Volume and Issue: unknown, P. gutjnl - 333880

Published: April 5, 2025

Background A rise in paediatric cases of acute hepatitis unknown origin (AHUO) was observed 2022, some requiring liver transplantation. link to adeno-associated virus 2 infection and CD4 + T-cell mediated disease reported cohorts the UK USA but does not explain all cases. Objective To determine intrahepatic immune cell interactions inflamed a possible contribution SARS-CoV-2 infection. Design Patients with non-A non-E (10/12 AHUO, 2/12 subacute) during February 2022–December 2022 undergoing biopsy were recruited European patient cohort. Hepatological, virological, histopathological highly multiplexed spatial single-cell analyses biopsies performed. Results negative for adenoviral PCR. Three patients had positive serology 10/12 history or serological evidence Imaging mass cytometry identified significant infiltration an enrichment CD8 T-cells. The highest concomitant peripheral activation most severe hepatitis. connected histomorphological interface bridging necrosis. Cellular neighbourhood analysis indicated disease-associated microanatomic between CX3CR1 endothelial myeloid populations, interacting effector T-cells suggesting pathogenic cellular triad. Of note, we detected antigens ACE2-expressing cells areas pathology 11/12 samples using several different detection methods. treated corticosteroid therapy no transplantation required. Conclusions We manifestation immune-mediated postacute sequel COVID-19 associated characteristic infiltrate children AHUO. testing should be considered

Language: Английский

Citations

1
Liver regeneration after injury: Mechanisms, cellular interactions and therapeutic innovations DOI Creative Commons
Qi Liu,

Senyan Wang,

Jing Fu

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(8)

Published: Aug. 1, 2024

The liver possesses a distinctive capacity for regeneration within the human body. Under normal circumstances, cells replicate themselves to maintain function. Compensatory replication of healthy hepatocytes is sufficient after acute injuries. In late stage chronic damage, large number die and hepatocyte blocked. Liver has more complex mechanisms, such as transdifferentiation between cell types or hepatic progenitor mediated. Dysregulation causes severe disease. Gaining comprehensive understanding mechanisms would facilitate advancement efficient therapeutic approaches. This review provides an overview signalling pathways linked different aspects in various diseases. Moreover, new knowledge on cellular interactions during regenerative process also presented. Finally, this paper explores potential applications technologies, nanotechnology, stem transplantation organoids, injury, offering fresh perspectives treating

Language: Английский

Citations

8
Hepatocyte-derived tissue extracellular vesicles safeguard liver regeneration and support regenerative therapy DOI Creative Commons
Si-Qi Ying, Yuan Cao,

Ze-Kai Zhou

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 30, 2024

Tissue-derived extracellular vesicles (EVs) are emerging as pivotal players to maintain organ homeostasis, which show promise a next-generation candidate for medical use with extensive source. However, the detailed function and therapeutic potential of tissue EVs remain insufficiently studied. Here, through bulk single-cell RNA sequencing analyses combined ultrastructural examinations, we first reveal that in situ liver (LT-EVs) contribute intricate regenerative process after partial hepatectomy (PHx), hepatocytes primary source regenerating liver. Nanoscale proteomic profiling further identify hepatocyte-specific (Hep-EVs) strengthened release carrying proliferative messages PHx. Moreover, targeted inhibition Hep-EV via AAV-shRab27a vivo confirms Hep-EVs required orchestrate regeneration. Mechanistically, from reciprocally stimulate hepatocyte proliferation by promoting cell cycle progression Cyclin-dependent kinase 1 (Cdk1) activity. Notably, supplementing demonstrates translational ameliorates insufficient This study provides functional mechanistic framework showing governs rapid regeneration, thereby enriching our understanding physiological endogenous regeneration therapy.

Language: Английский

Citations

7
Biomarker discovery in acetaminophen hepatotoxicity: leveraging single-cell transcriptomics and mechanistic insight DOI
David S. Umbaugh, Hartmut Jaeschke

Expert Review of Clinical Pharmacology, Journal Year: 2024, Volume and Issue: 17(2), P. 143 - 155

Published: Jan. 13, 2024

Introduction Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury and can a rapid progression to acute failure (ALF). Therefore, identification prognostic biomarkers determine which patients will require transplant critical for APAP-induced ALF.

Language: Английский

Citations

6
3D printing incorporating gold nanozymes with mesenchymal stem cell-derived hepatic spheroids for acute liver failure treatment DOI
Yuanyuan Jin, Jiabin Zhang,

Xiaodie Chen

et al.

Biomaterials, Journal Year: 2024, Volume and Issue: 315, P. 122895 - 122895

Published: Oct. 19, 2024

Language: Английский

Citations

5