TREM2 promotes the formation of a tumor-supportive microenvironment in hepatocellular carcinoma DOI Creative Commons

Hanrui Guo,

Meiling Wang, Cai‐Fang Ni

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Jan. 21, 2025

Abstract Background Triggering receptor expressed on myeloid cells 2 (TREM2), a surface predominantly cells, is major hub gene in pathology-induced immune signaling. However, its function hepatocellular carcinoma (HCC) remains controversial. This study aimed to evaluate the role of TREM2 tumor microenvironment context HCC progression. Methods was experimentally induced wild-type (WT) and Trem2 -deficient ( −/− ) mice, clinical sample analysis vitro studies macrophages were conducted. treated with conditioned medium from WT or macrophages, their malignant phenotypes underlying mechanisms analyzed. Results deficiency reduced liver burden orthotopic subcutaneous models by altering CD8 + T cell infiltration. presented increased chemokine secretion. TGF-β1 found be positively correlated expression HCC, TGF-β blockade reversed induction. On other hand, associated glycolysis PKM2 cells; this association may related secretion IL-1β, which enhances cells. Conclusions These results reveal that play driving progression suppressing infiltration promoting glycolysis, providing new therapeutic target for HCC.

Language: Английский

An adipocentric perspective on the development and progression of non-alcoholic fatty liver disease DOI Creative Commons
Eun Young Lee, Hannelie Korf, António Vidal-Puig

et al.

Journal of Hepatology, Journal Year: 2023, Volume and Issue: 78(5), P. 1048 - 1062

Published: Feb. 3, 2023

Alongside the liver, white adipose tissue (WAT) is critical in regulating systemic energy homeostasis. Although each organ has its specialised functions, they must work coordinately to regulate whole-body metabolism. Adipose tissues and liver are relatively resilient can adapt an surplus by facilitating triglyceride (TG) storage up a certain threshold level without significant metabolic disturbances. However, lipid WAT beyond "personalised" adiposity becomes dysfunctional, leading inflexibility, progressive inflammation, aberrant adipokine secretion. Moreover, failure of store mobilise lipids results knock-on overload, particularly liver. Factors contributing hepatic overload include released from WAT, dietary fat intake, enhanced de novo lipogenesis. In contrast, extrahepatic mechanisms counteracting toxic entail coordinated compensation through oxidation fatty acids brown as TGs WAT. Failure these integrated homeostatic leads quantitative increases qualitative alterations lipidome Initially, hepatocytes preferentially accumulate TG species "benign" non-alcoholic with time, inflammatory responses ensue, progressing into more severe conditions such steatohepatitis, cirrhosis, hepatocellular carcinoma, some individuals (often early prognostic clue). Herein, we highlight pathogenic importance obesity-induced "adipose failure", resulting decreased functionality (i.e. capacity flexibility), development progression NAFL/NASH.

Language: Английский

Citations

102
Extracellular vesicles in fatty liver promote a metastatic tumor microenvironment DOI
Zhijun Wang, So Yeon Kim, Wei Tu

et al.

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(7), P. 1209 - 1226.e13

Published: May 11, 2023

Language: Английский

Citations

78
Hepatic danger signaling triggers TREM2 + macrophage induction and drives steatohepatitis via MS4A7-dependent inflammasome activation DOI
Linkang Zhou, Xiaoxue Qiu, Ziyi Meng

et al.

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(738)

Published: March 13, 2024

Metabolic dysfunction–associated steatohepatitis (MASH), formerly known as nonalcoholic (NASH), is an advanced stage of metabolic fatty liver disease. The pathogenic mechanisms MASH center on hepatocyte injury and the ensuing immune response within microenvironment. Recent work has implicated TREM2 + macrophages in various disease conditions, substantial induction NASH-associated (NAMs) serves a hallmark Despite this, through which NAMs contribute to pathogenesis remain poorly understood. Here, we identify membrane-spanning 4-domains a7 (MS4A7) NAM-specific factor that exacerbates progression mice. Hepatic MS4A7 expression was strongly induced mouse human associated with severity injury. Whole-body myeloid-specific ablation Ms4a7 alleviated diet-induced pathologies male We demonstrate exposure lipid droplets (LDs), released upon steatotic hepatocytes, triggered NAM exacerbated MASH-associated MS4A7-dependent manner. Mechanistically, drove NLRP3 inflammasome activation via direct physical interaction shaped disease-associated cell states This reveals LD-MS4A7-NLRP3 axis driver provides insights into role pathogenesis.

Language: Английский

Citations

17
Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets DOI Creative Commons

Fan Guan,

Ruixuan Wang,

Zhenjie Yi

et al.

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

Published: March 7, 2025

Abstract Macrophages are immune cells belonging to the mononuclear phagocyte system. They play crucial roles in defense, surveillance, and homeostasis. This review systematically discusses types of hematopoietic progenitors that give rise macrophages, including primitive progenitors, erythro-myeloid stem cells. These have distinct genetic backgrounds developmental processes. Accordingly, macrophages exhibit complex diverse functions body, phagocytosis clearance cellular debris, antigen presentation, response, regulation inflammation cytokine production, tissue remodeling repair, multi-level regulatory signaling pathways/crosstalk involved homeostasis physiology. Besides, tumor-associated a key component TME, exhibiting both anti-tumor pro-tumor properties. Furthermore, functional status is closely linked development various diseases, cancer, autoimmune disorders, cardiovascular disease, neurodegenerative metabolic conditions, trauma. Targeting has emerged as promising therapeutic strategy these contexts. Clinical trials macrophage-based targeted drugs, immunotherapies, nanoparticle-based therapy were comprehensively summarized. Potential challenges future directions targeting also been discussed. Overall, our highlights significance this versatile cell human health which expected inform research clinical practice.

Language: Английский

Citations

3
The muscle-enriched myokine Musclin impairs beige fat thermogenesis and systemic energy homeostasis via Tfr1/PKA signaling in male mice DOI Creative Commons
Lu Jin, Shuang Han, Xue Lv

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 19, 2023

Abstract Skeletal muscle and thermogenic adipose tissue are both critical for the maintenance of body temperature in mammals. However, whether these two tissues interconnected to modulate thermogenesis metabolic homeostasis response thermal stress remains inconclusive. Here, we report that human mouse obesity is associated with elevated Musclin levels circulation. Intriguingly, expression markedly increased or decreased when male mice housed thermoneutral chronic cool conditions, respectively. Beige fat then identified as primary site action. Muscle-transgenic AAV-mediated overexpression attenuates beige thermogenesis, thereby exacerbating diet-induced disorders mice. Conversely, inactivation by muscle-specific ablation neutralizing antibody treatment promotes improves Mechanistically, binds transferrin receptor 1 (Tfr1) antagonizes Tfr1-mediated cAMP/PKA-dependent induction adipocytes. This work defines temperature-sensitive myokine a negative regulator exacerbates deterioration health obese thus provides framework therapeutic targeting this endocrine pathway.

Language: Английский

Citations

28
Neuregulin 4 as a novel adipokine in energy metabolism DOI Creative Commons
Yuanbin Liu, Mingkai Chen

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 10, 2023

Adipose tissue has been shown to play a key role in energy metabolism and it regulate metabolic homeostasis through the secretion of adipokines. Neuregulin 4 (Nrg4), novel adipokine secreted mainly by brown adipose (BAT), recently characterized as having an important effect on regulation glucolipid metabolism. Nrg4 can modulate BAT-related thermogenesis increasing sympathetic innervation therefore potential benefits. improves dysregulation various diseases such insulin resistance, obesity, non-alcoholic fatty liver disease, diabetes several mechanisms anti-inflammation, autophagy regulation, pro-angiogenesis, lipid normalization. However, inconsistent findings are found regarding effects clinical settings, this heterogeneity needs be further clarified future studies. The protective suggests that may promising endocrine therapeutic target.

Language: Английский

Citations

25
Myocardial infarction accelerates the progression of MASH by triggering immunoinflammatory response and induction of periosti DOI
Xie Wei, Jing Gan, Xiaodong Zhou

et al.

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(6), P. 1269 - 1286.e9

Published: June 1, 2024

Language: Английский

Citations

13
Integrated traditional Chinese and Western medicine in the prevention and treatment of non-alcoholic fatty liver disease: future directions and strategies DOI Creative Commons
Xin Ding, Xu He,

Bulang Tang

et al.

Chinese Medicine, Journal Year: 2024, Volume and Issue: 19(1)

Published: Feb. 3, 2024

Abstract Traditional Chinese medicine (TCM) has been widely used for several centuries metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). At present, NAFLD become the most prevalent form of chronic worldwide and can progress to steatohepatitis (NASH), cirrhosis, even hepatocellular carcinoma. However, there is still a lack effective treatment strategies in Western medicine. The development driven by multiple mechanisms, genetic factors, insulin resistance, lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, inflammation, gut microbiota dysbiosis, adipose tissue dysfunction. Currently, certain drugs, sensitizers, statins, vitamin E, ursodeoxycholic acid betaine, are proven be beneficial clinical NAFLD. Due its complex pathogenesis, personalized that integrates various mechanisms may provide better benefits patients with holistic view syndrome differentiation TCM have advantages treating NAFLD, which similar principles In TCM, primarily classified into five types based on experience. It located closely related spleen kidney functions. due multi-component characteristics traditional medicine, application considerably limited. this review, we summarize advances pathogenesis drawn from both perspectives. We highlight complementary should receive increased attention prevention

Language: Английский

Citations

12
The secretory function of adipose tissues in metabolic regulation DOI Creative Commons
Yang Liu, Shuwen Qian, Yan Tang

et al.

Life Metabolism, Journal Year: 2024, Volume and Issue: 3(2)

Published: Jan. 20, 2024

In addition to their pivotal roles in energy storage and expenditure, adipose tissues play a crucial part the secretion of bioactive molecules, including peptides, lipids, metabolites, extracellular vesicles, response physiological stimulation metabolic stress. These secretory factors, through autocrine paracrine mechanisms, regulate various processes within tissues. include adipogenesis, glucose lipid metabolism, inflammation, adaptive thermogenesis, all which are essential for maintenance balance functionality tissue micro-environment. A subset these adipose-derived factors can enter circulation target distant appetite, cognitive function, insulin sensitivity, gluconeogenesis, cardiovascular remodeling, exercise capacity. this review, we highlight role signaling pathways modulating homeostasis. Furthermore, delve into alterations both content under pathological conditions, shedding light on potential pharmacological treatment strategies related diseases.

Language: Английский

Citations

11
Myeloid Trem2 ameliorates the progression of metabolic dysfunction-associated steatotic liver disease by regulating macrophage pyroptosis and inflammation resolution DOI Creative Commons
Wenjie Yu, Yu Zhang,

Linfeng Sun

et al.

Metabolism, Journal Year: 2024, Volume and Issue: 155, P. 155911 - 155911

Published: April 10, 2024

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing year by and has become one the leading causes end-stage worldwide. Triggering Receptor Expressed on Myeloid Cells 2 (Trem2) been confirmed to play an essential role in progression MASLD, but its specific mechanism still needs be clarified. This study aims explore Trem2 MASLD.

Language: Английский

Citations

10