SIRT2 regulates oxidative stress response in liver fibrosis mice through the NLRP3 inflammasome pathway DOI Creative Commons
Jingru Guo,

Junshu Nie,

Dongni Li

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 17, 2023

Abstract Liver fibrosis is a crucial step in the progression of various chronic liver diseases to cirrhosis, which can affect prognosis diseases. The NAD + dependent deacetylase sirtuins family member SIRT2 regulate inflammatory corpuscular pathway pathological processes, but its related mechanism not yet clear. This study established models wild-type and knockout mice, evaluated their effects on homeostasis using immunoblotting, immunofluorescence, histopathological staining methods. results indicate that deletion gene enhances NLRP3 acetylation, activates inflammasome pathway, accelerates oxidative stress. These findings suggest may be potential target for regulating restoring health.

Language: Английский

Liver macrophages revisited: The expanding universe of versatile responses in a spatiotemporal context DOI Creative Commons
Adrien Guillot, Frank Tacke

Hepatology Communications, Journal Year: 2024, Volume and Issue: 8(7)

Published: July 1, 2024

The liver is a vital organ that continuously adapts to wide and dynamic diversity of self-antigens xenobiotics. This involves the active contribution immune cells, particularly by liver-resident macrophages, Kupffer cells (KCs), which exert variety central functions in homeostasis disease. As such, KCs interact with their microenvironment shape hepatic cellular landscape, control gut-derived signal integration, modulate metabolism. On injury, rapid recruitment bone marrow monocyte-derived macrophages alters this status quo and, when unrestrained, drastically compromises homeostasis, surveillance, tissue organization. Several factors determine functional roles these processes, such as ontogeny, activation/polarization profile importantly, spatial distribution within liver. Loss tolerance adaptability environment may result persistent inflammation, fibrosis, cirrhosis, tumorigenic niche promoting cancer. In review, we aim at providing most recent breakthroughs our understanding macrophage biology, spatiotemporal context, well on potential therapeutic interventions hold key tackling remaining clinical challenges varying etiologies hepatology.

Language: Английский

Citations

9
CCR2 signaling regulates anti-chlamydia T cell immune responses in the airway DOI Creative Commons

Shuaini Yang,

Jinxi Yu,

Xue Dong

et al.

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(2), P. e1012912 - e1012912

Published: Feb. 4, 2025

CCR2, a member of the G protein-coupled receptor (GPCR) superfamily, is widely expressed on monocytes, macrophages, activated T cells, and other cell types, plays critical role in coordinating immune response to various infections. Here we demonstrate that CCR2 expression significantly elevated during Chlamydia muridarum ( C . ) respiratory infection, its absence leads exacerbated susceptibility, as evidenced by significant weight loss, higher bacterial loads, severe lung pathology, levels inflammatory cytokines il-1β , tnfα il-6 ). The ccr2 impairs both myeloid infiltration responses, which are crucial for effective defense. Specifically, deficiency disrupts differentiation Th1 primary effector lineage responsible clearing chlamydia through secretion interferon-gamma (IFN-γ). As result, there decrease CD3 + CD4 IFN-γ cells spleen, accompanied reduced protein mRNA, well downregulated mRNA Th1-promoting il-12p35 il-12p40 transcription factors stat4 T-bet ), play roles differentiation. Moreover, greatly diminishes STAT1 phosphorylation, key regulator cells. Meanwhile, also observed reduction CD8 following deficiency. Conversely, -/- mice exhibit an exaggerated Th2-type response, with Th2-promoting (IL-4), (STAT6 gata3 il-5 together lead more tissue damage increased susceptibility infection. Furthermore, these show IL-17 along enhanced Th17-type characterized Th17-promoting TGFB stat3 RORγt il-21 suggesting compensatory mechanism drives neutrophil exacerbate inflammation. These findings underscore pivotal chemokine receptor, orchestrating infection facilitating while restraining thereby alleviating pulmonary

Language: Английский

Citations

1
NUP85 alleviates lipid metabolism and inflammation by regulating PI3K/AKT signaling pathway in nonalcoholic fatty liver disease DOI Creative Commons

Yincui Wu,

Qi Yan,

Si-qing Yue

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(6), P. 2219 - 2235

Published: Jan. 1, 2024

Nonalcoholic fatty liver disease (NAFLD) is one of the common causes chronic in world.The problem NAFLD had become increasingly prominent.However, its pathogenesis still indistinct.As we all know, begins with accumulation triglyceride (TG), leading to degeneration, inflammation and other tissues damage.Notably, structure nucleoporin 85 (NUP85) related lipid metabolism diseases.In this study, results researches indicated that NUP85 played a critical role NAFLD.Firstly, expression level methionine-choline-deficient (MCD)-induced mice increased distinctly, as well levels fat disorder inflammation.On contrary, knockdown opposite effects.In vitro, AML-12 cells were stimulated 2 mm free acids (FFA) for 24 h.Results also proved significantly model group, level.Besides, protein could interact C-C motif chemokine receptor (CCR2).Furthermore, when expressed at an extremely low level, CCR2 decreased, accompanied inhibition phosphorylation phosphoinositol-3 kinase (PI3K)-protein B (AKT) signaling pathway.What more, trans isomer (ISRIB), targeted inhibitor NUP85, alleviate NAFLD.In summary, our findings suggested functions important regulator through modulation CCR2.

Language: Английский

Citations

8
Identification and characterization of endogenous retroviruses upon SARS-CoV-2 infection DOI Creative Commons
Xuefei Guo, Yang Zhao, Fuping You

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 5, 2024

Endogenous retroviruses (ERVs) derived from the long terminal repeat (LTR) family of transposons constitute a significant portion mammalian genome, with origins tracing back to ancient viral infections. Despite comprising approximately 8% human specific role ERVs in pathogenesis COVID-19 remains unclear. In this study, we conducted genome-wide identification peripheral blood mononuclear cells (hPBMCs) and primary lung epithelial monkeys mice, both infected uninfected SARS-CoV-2. We identified 405, 283, 206 significantly up-regulated transposable elements (TEs) hPBMCs, monkeys, respectively. This included 254, 119, 68, 28 found hPBMCs severe mild patients, transgenic mice expressing ACE2 receptor (hACE2) Furthermore, analysis using Genomic Regions Enrichment Annotations Tool (GREAT) revealed certain parental genomic sequences these patients may be involved various biological processes, including histone modification replication. Of particular interest, 210 specifically group. The genes associated differentially expressed were enriched processes such as immune response activation modification. HERV1_I-int: ERV1:LTR LTR7Y: highlighted potential biomarkers for evaluating severity COVID-19. Additionally, validation our findings RT-qPCR Bone Marrow-Derived Macrophages (BMDMs) by HSV-1 VSV provided further support results. study offers insights into expression patterns roles following infection, providing valuable resource future studies on their interaction

Language: Английский

Citations

6
Liver cirrhosis: molecular mechanisms and therapeutic interventions DOI Creative Commons
Zihe Dong, Yeying Wang, Weilin Jin

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(10)

Published: Sept. 17, 2024

Liver cirrhosis is the end-stage of chronic liver disease, characterized by inflammation, necrosis, advanced fibrosis, and regenerative nodule formation. Long-term inflammation can cause continuous damage to tissues hepatocytes, along with increased vascular tone portal hypertension. Among them, fibrosis necessary stage essential feature cirrhosis, effective antifibrosis strategies are commonly considered key treating cirrhosis. Although different therapeutic aimed at reversing or preventing have been developed, effects not be more satisfactory. In this review, we discussed abnormal changes in microenvironment that contribute progression highlighted importance recent strategies, including lifestyle improvement, small molecular agents, traditional Chinese medicine, stem cells, extracellular vesicles, gut remediation, regulate Meanwhile, for nanoparticles discussed, as their possible underlying broad application prospects ameliorating Finally, also reviewed major challenges opportunities nanomedicine‒biological environment interactions. We hope review will provide insights into pathogenesis mechanisms thus facilitating new methods, drug discovery, better treatment

Language: Английский

Citations

5
Extracellular vesicles from mesenchymal stem cells improve liver injury in rats with mild liver damage. Underlying mechanisms and role of TGFβ DOI
Gergana Mincheva, Victoria Moreno‐Manzano, Vicente Felipo

et al.

Life Sciences, Journal Year: 2025, Volume and Issue: 364, P. 123429 - 123429

Published: Jan. 28, 2025

Language: Английский

Citations

0
The role and therapeutic targeting of the CCL2/CCR2 signaling axis in inflammatory and fibrotic diseases DOI Creative Commons

Shan Guo,

Qi Zhang, Yingjie Guo

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 9, 2025

CCL2, a pivotal cytokine within the chemokine family, functions by binding to its receptor CCR2. The CCL2/CCR2 signaling pathway plays crucial role in development of fibrosis across multiple organ systems modulating recruitment and activation immune cells, which turn influences progression fibrotic diseases liver, intestines, pancreas, heart, lungs, kidneys, other organs. This paper introduces biological CCL2 CCR2, highlighting their similarities differences concerning disorders various systems, reviews recent progress diagnosis treatment clinical linked pathway. Additionally, further in-depth research is needed explore significance axis conditions affecting different

Language: Английский

Citations

0
The role of macrophages in liver fibrosis: composition, heterogeneity, and therapeutic strategies DOI Creative Commons

Xiaocao Ma,

Jia Qiu,

Shubiao Zou

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 20, 2024

Macrophages, the predominant immune cells in liver, are essential for maintaining hepatic homeostasis and responding to liver injury caused by external stressors. The macrophage population is highly heterogeneous plastic, mainly comprised of resident kuffer (KCs), monocyte-derived macrophages (MoMφs), lipid-associated (LAMs), capsular (LCMs). KCs, a macrophages, localized can self-renew through situ proliferation. However, MoMφs recruited from periphery circulation. LAMs self-renewing subgroup near bile duct. While LCMs located capsule derived peripheral monocytes. also involved damage induced various factors. Hepatic exhibit distinct phenotypes functions depending on specific microenvironment liver. KCs critical initiating inflammatory responses after sensing tissue damage, while infiltrated implicated both progression resolution chronic inflammation fibrosis. regulatory function fibrosis has attracted significant interest current research. Numerous literatures have documented that dual impact be categorized into two subtypes based their Ly-6C expression level: with high (referred as hi macrophages) reparative low lo macrophages). conducive occurrence fibrosis, associated degradation extracellular matrix (ECM) regression Given this, play pivotal role occurrence, progression, Based these studies, treatment therapies targeting being studied gradually. This review aims summarize researches composition origin heterogeneity anti-fibrosis therapeutic strategies

Language: Английский

Citations

2
Navigating the liver landscape: upcoming pharmacotherapies for primary sclerosing cholangitis DOI
Hoang Nam Pham, Linh Pham, Keisaku Sato

et al.

Expert Opinion on Pharmacotherapy, Journal Year: 2024, Volume and Issue: 25(7), P. 895 - 906

Published: May 2, 2024

Introduction Primary sclerosing cholangitis (PSC) is a bile duct disorder characterized by ductular reaction, hepatic inflammation, and liver fibrosis. The pathogenesis of PSC still undefined, treatment options for patients are limited. Previous clinical trials evaluated drug candidates targeting various cellular functions pathways, such as acid signaling absorption, gut bacteria permeability, lipid metabolisms. However, most phase III were disappointing, except vancomycin therapy, there no established medications with efficacy safety confirmed IV trials.

Language: Английский

Citations

1
Editorial: Community series in hepatic immune response underlying liver cirrhosis and portal hypertension, volume II DOI Creative Commons
Tian Lan, Sheyu Li, Haopeng Yu

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 11, 2023

EDITORIAL article Front. Immunol., 11 October 2023Sec. Molecular Innate Immunity Volume 14 - 2023 | https://doi.org/10.3389/fimmu.2023.1305666

Language: Английский

Citations

0