Cellular Signalling, Год журнала: 2023, Номер 108, С. 110727 - 110727
Опубликована: Май 29, 2023
Язык: Английский
MedComm, Год журнала: 2024, Номер 5(8)
Опубликована: Авг. 1, 2024
Abstract Macrophages are versatile immune cells with remarkable plasticity, enabling them to adapt diverse tissue microenvironments and perform various functions. Traditionally categorized into classically activated (M1) alternatively (M2) phenotypes, recent advances have revealed a spectrum of macrophage activation states that extend beyond this dichotomy. The complex interplay signaling pathways, transcriptional regulators, epigenetic modifications orchestrates polarization, allowing respond stimuli dynamically. Here, we provide comprehensive overview the cascades governing focusing on roles Toll‐like receptors, signal transducer activator transcription proteins, nuclear microRNAs. We also discuss emerging concepts metabolic reprogramming trained immunity, contributing their functional adaptability. Macrophage plasticity plays pivotal role in repair regeneration, macrophages coordinating inflammation, angiogenesis, matrix remodeling restore homeostasis. By harnessing potential novel therapeutic strategies targeting polarization could be developed for diseases, including chronic wounds, fibrotic disorders, inflammatory conditions. Ultimately, deeper understanding molecular mechanisms underpinning will pave way innovative regenerative medicine engineering approaches.
Язык: Английский
Процитировано
38
Nature Genetics, Год журнала: 2024, Номер 56(5), С. 953 - 969
Опубликована: Апрель 16, 2024
Язык: Английский
Процитировано
19
Hepatology, Год журнала: 2023, Номер 79(3), С. 589 - 605
Опубликована: Сен. 9, 2023
Background and Aims: Immune cells play a crucial role in liver aging. However, the impact of dynamic changes local immune microenvironment on age-related injury remains poorly understood. We aimed to characterize intrahepatic at different ages investigate key mechanisms associated with Approach Results: carried out single-cell RNA sequencing mouse tissues 4 ages, namely, newborn, suckling, young, aged stages. The transcriptomic landscape, cellular classification, intercellular communication were analyzed. confirmed findings by multiplex immunofluorescence staining, flow cytometry, vitro functional experiments, chimeric animal models. Nine subsets 89,542 unique properties identified, which Cxcl2 + macrophages within monocyte/macrophage subset preferentially enriched liver. presented senescence-associated secretory phenotype recruited neutrophils through CXCL2-CXCR2 axis. Through secretion IL-1β TNF-α, stimulated neutrophil extracellular traps formation. Targeting axis limited migration toward attenuated injury. Moreover, relationship between was further validated human transplantation samples. Conclusions: This in-depth study illustrates that mechanism macrophage-driven activation involves provides potential therapeutic strategy for
Язык: Английский
Процитировано
34
Experimental Hematology and Oncology, Год журнала: 2024, Номер 13(1)
Опубликована: Июнь 18, 2024
Abstract Interleukin-6 (IL-6) is a pleiotropic cytokine and exerts its complex biological functions mainly through three different signal modes, called cis- , trans- cluster signaling. When IL-6 binds to membrane or soluble receptors, the co-receptor gp130 activated initiate downstream signaling induce expression of target genes. In liver, can perform anti-inflammatory activities promote hepatocyte reprogramming liver regeneration. On contrary, also pro-inflammatory aging, fibrosis, steatosis, carcinogenesis. However, understanding roles underlying mechanisms in physiological pathological processes still an ongoing process. So far, therapeutic agents against IL‑6, IL‑6 receptor (IL‑6R), IL-6-sIL-6R complex, transducers have been developed, determined be effective intervention inflammatory diseases cancers. this review, we summarized highlighted double-edged effects homeostasis, inflammation, chronic diseases, for better shifting “negative” “beneficial” actions, further discussed potential targeting clinics.
Язык: Английский
Процитировано
13
Cell stem cell, Год журнала: 2024, Номер 31(7), С. 949 - 960
Опубликована: Июль 1, 2024
Язык: Английский
Процитировано
13
Nature Communications, Год журнала: 2024, Номер 15(1)
Опубликована: Фев. 26, 2024
Tissue damage elicits cell fate switching through a process called metaplasia, but how the starting is silenced and new activated has not been investigated in animals. In culture, pioneer transcription factors mediate "reprogramming" by opening chromatin sites for expression that can attract from cell's enhancers. Here we report SOX4 sufficient to initiate hepatobiliary metaplasia adult mouse liver, closely mimicking initiated toxic liver. lineage-traced cells, assessed timing of SOX4-mediated enhancer versus decommissioning. Initially, directly binds closes hepatocyte regulatory sequences via an overlapping motif with HNF4A, master factor. Subsequently, exerts factor activity open biliary sequences. The results delineate hierarchy which gene networks become reprogrammed under physiological conditions, providing deeper insight into basis transitions
Язык: Английский
Процитировано
12
Nature Genetics, Год журнала: 2024, Номер 56(5), С. 938 - 952
Опубликована: Апрель 16, 2024
Язык: Английский
Процитировано
12
Cell stem cell, Год журнала: 2024, Номер 31(9), С. 1244 - 1261
Опубликована: Авг. 19, 2024
Язык: Английский
Процитировано
10
Nature Genetics, Год журнала: 2025, Номер unknown
Опубликована: Фев. 13, 2025
Abstract Cell fate plasticity enables development, yet unlocked is a cancer hallmark. While transcription master regulators induce lineage-specific genes to restrict plasticity, it remains unclear whether actively suppressed by repressors. Here we computationally predict so-called safeguard repressors for 18 cell types that block phenotypic lifelong. We validated hepatocyte-specific candidates using reprogramming, revealing prospero homeobox protein 1 (PROX1) enhanced hepatocyte identity direct repression of alternative regulators. In mice, Prox1 was required efficient regeneration after injury and sufficient prevent liver tumorigenesis. line with patient data, depletion caused loss in vivo enabled the transition hepatocellular carcinoma cholangiocarcinoma. Conversely, overexpression promoted cholangiocarcinoma transdifferentiation. Our findings provide evidence PROX1 as support model where cell-type-specific suppress throughout life lineage thus disease.
Язык: Английский
Процитировано
2
Journal of Medical Virology, Год журнала: 2025, Номер 97(1)
Опубликована: Янв. 1, 2025
SARS-CoV-2 infection is accompanied by elevated liver enzymes, and patients with pre-existing conditions experience more severe disease. While it was known that infects human hepatocytes, our study determines the mechanism of infection, demonstrates viral replication spread, highlights direct hepatocyte damage. Viral readily detectable upon primary hepatocytes hepatoma cells ancestral SARS-CoV-2, Delta, Omicron variants. Hepatocytes express receptor ACE2 host cell protease TMPRSS2, knocking down TMPRSS2 impaired infection. Progeny viruses released from infected showed typical coronavirus morphology electron microscopy proved infectious when transferred to fresh cells, indicating can contribute virus spread. Importantly, rapidly induced death in a replication-dependent fashion, variant showing faster onset but less extensive death. C57BL/6 wild-type mice mouse-adapted strain high levels RNA lung tissues. ALT peaked cleared liver. Liver histology revealed profound tissue damage immune infiltration, cytopathic effects immune-mediated killing pathology.
Язык: Английский
Процитировано
1