Elucidating TREM2's Role in Proliferative Diabetic Retinopathy: A Transcriptomic Approach DOI Creative Commons

Qi Liu,

Ya-Ni Wu,

Wan-Zhao Yi

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 12, 2024

Abstract Background Proliferative diabetic retinopathy (PDR) is a leading cause of vision loss in patients. This study aims to identify novel biomarkers for PDR progression using next-generation sequencing (NGS) transcriptome analysis. Methods We conducted weighted gene co-expression network analysis (WGCNA) on RNA-seq data from 43 post-mortem donor retinas key modules associated with (DR) stages. Differential expression was performed transcriptomes patients and healthy controls. Protein levels retinal tissues streptozotocin (STZ)-induced mouse model were validated immunofluorescence Western blot analyses. Results WGCNA identified the "MEyellow" module, comprising 231 genes, as significantly PDR. Intersection differentially expressed genes revealed 29 common both datasets. Gene ontology (GO) highlighted biological significance these particularly TREM2. Immunofluorescence analyses confirmed upregulation TREM2 microglial marker IBA-1 STZ-induced mice, corroborating its critical role. Conclusions implicated pathogenesis PDR, underscoring potential therapeutic target mitigate disease progression.

Language: Английский

Role of triggering receptor expressed on myeloid cells 2 in the pathogenesis of non-alcoholic fatty liver disease DOI
Lihui Zhang, Sutong Liu, Qing Zhao

et al.

World Journal of Hepatology, Journal Year: 2025, Volume and Issue: 17(2)

Published: Feb. 20, 2025

Non-alcoholic fatty liver disease (NAFLD) is a progressive disease. Without effective interventions, NAFLD can gradually develop to non-alcoholic steatohepatitis, fibrosis, cirrhosis and even hepatocellular carcinoma. It still investigate the precise molecular mechanism behind pathophysiology of NAFLD. Triggering receptor expressed on myeloid cells 2 (TREM2) sense tissue injury mediate immune remodeling, thereby inducing phagocytosis, lipid metabolism, metabolic transfer, promoting cell survival combating inflammatory activation. might as result TREM2's regulatory role. We here briefly summarize biological characteristics TREM2 its functions in progression Moreover, we propose broaden therapeutic strategy for by targeting TREM2.

Language: Английский

Citations

0
TREM2 Activation Relieves TMJOA by Stabilizing the Synovial Barrier via Siglec1 DOI
Xinhui Liu, Xinyue Luo, Mang Xiao

et al.

Journal of Dental Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Triggering receptor expressed on myeloid cells 2 (TREM2) is an immune that plays a vital role in innate responses. This study aims to investigate the effect of TREM2 synovial barrier homeostasis and synovitis during temporomandibular joint osteoarthritis (TMJOA). The expression level decreased synovium both patients with TMJOA mouse model TMJOA, accompanied by breakdown. overexpression inhibits macrophage inflammatory response ex vivo relieves inflammation, cartilage degeneration, destruction monosodium iodoacetate–induced mice. RNA-seq analysis reveals Siglec1 serves as downstream signal downregulated after activation. Further vitro experiments demonstrate rhSiglec1 treatment promotes synthesis release cytokines, such interleukin-6 RANTES, macrophages reverses alleviation activation disorders, degradation, bone destruction. Overall, this verifies alleviates pathology maintaining inhibiting inflammation. These findings provide new insight into mechanism pathogenesis TMJOA.

Language: Английский

Citations

0
Antibody-Induced TREM2 Ectodomain Shedding Inhibits TREM2 Signaling in Macrophage DOI
Wenxing Li, Hui Jin,

Yating Xu

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: unknown, P. 151674 - 151674

Published: March 1, 2025

Language: Английский

Citations

0
The dual role of CXCL9/SPP1 polarized tumor-associated macrophages in modulating anti-tumor immunity in hepatocellular carcinoma DOI Creative Commons
Yu Gu, Zhihui Zhang, Hao Huang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 31, 2025

Introduction The main challenge for cancer therapy lies in immuno-suppressive tumor micro-environment. Reprogramming tumor-associated macrophages (TAMs) into an anti-tumor phenotype is a promising strategy. Methods A comprehensive analysis by combing multi-regional single-cell, bulk and spatial transcriptome profiling with radiomics characterization was conducted to dissect the heterogeneity of TAMs resolve landscape CXCL9:SPP1 (CS) macrophage polarity HCC. Results were particularly increased SPP1 + CXCL9 identified as dominant subtypes different evolutionary trajectories. TAMs, located core, co-localized cancer-associated fibroblasts promote growth further contributed worse prognosis. In contrast, peritumoral region, synergized CD8 T cells create immunostimulatory For first time, we explored applicability CS HCC tumors revealed several key transcription factors involved shaping this polarity. Moreover, could serve potential indicator prognostic micro-environmental status patients. Based on medical imaging data, developed tool, RCSP (Radiogenomics-based CXCL9/SPP1 Polarity), assist non-invasively predicting Conclusion Our research sheds light regulatory roles micro-environment provides new therapeutic targets or insights reprogramming targeted

Language: Английский

Citations

0
Single‐cell and spatial omics unravel the spatiotemporal biology of tumour border invasion and haematogenous metastasis DOI Creative Commons
Xifu Cheng, Yuke Cao, Xiangyi Liu

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(10)

Published: Sept. 30, 2024

Language: Английский

Citations

3
Single-cell RNA sequencing reveals immune microenvironment niche transitions during the invasive and metastatic processes of ground-glass nodules and part-solid nodules in lung adenocarcinoma DOI Creative Commons
Yifeng Ren,

Qiong Ma,

Xiao Zeng

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Nov. 23, 2024

Radiographically, ground-glass nodules (GGN) and part-solid (PSN) in lung adenocarcinoma (LUAD) have significant heterogeneity their clinical manifestations, biological characteristics, prognosis. This study aimed to explore the of LUAD different radiological phenotypes associated factors influencing tumor evolution. We performed single-cell RNA sequencing (scRNA-seq) on tissues from eight seven cases GGN– PSN–LUAD, respectively, at disease stages, including minimally invasive (MIA), (IAC), metastatic cancer (MLC). Additionally, we analyzed adjacent normal four cases. Immunohistochemistry, multiplex immunofluorescence, external scRNA-seq data were employed confirm expression signature genes as well distribution patterns CXCL9 + TAMs TREM2 TAMs. A mouse model was generated using gene editing, organoid culture, orthotopic transplantation techniques, comprehensive analyses such histopathology, sequencing, Western blotting validate key pathways. Diverse cellular compositions observed microenvironment (TME) during PSN–LUAD invasion metastasis. Notably, tumor-associated macrophages (TAMs) exhibited most enrichment changes. It found that GGN–LUAD a stronger immune response than with increased interaction between CD8 tissue-resident memory T cells stage (MIA–IAC). Conversely, greater interactions MLC stage. differentiate into /SPP1 /SPP1– which promotes progression. also emphasizes transdifferentiation process IFN-γ activates STAT1 signaling pathway regulate activation TAMs, further recruiting Trm activating through MHC class I antigen presentation. The role IFN-γ/STAT1 occurrence development validated by animal experiments. Our findings offer potential therapeutic strategy maintain dynamic balance within TME improve immunotherapy efficacy modulating relative proportions functional states

Language: Английский

Citations

3
Upregulation of GZMK, TREM2, and OR4D10 as Prognostic Biomarkers in Thyroid Cancer: A Pan-Cancer and TCGA Data Analysis DOI Open Access

Nengping Zhu,

Liangliang Cai,

Qian Li

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3887 - 3887

Published: April 20, 2025

The study of gene anomalies linked to thyroid cancer is gaining more and attention, these molecular indicators can offer scholarly support for diagnosis, therapy selection, prognosis. Genotype-tissue expression pan-cancer data Cancer Genome Atlas (TCGA) were used investigate the GZMK, TREM2, OR4D10. In order assess relationship between OR4D10 patient outcome, TCGA clinical survival used. We clusterProfiler R software tool conduct enrichment analysis Moreover, database was immune cell infiltration expression. strongly expressed in several kinds malignancies including cancer. Gene sets related proliferation that are involved leukocyte cell-cell adhesion mononuclear differentiation significantly correlated with high Additional investigation revealed a correlation T DC (dendritic cell) scores According our research, OR4D10, GZMK could all be genes associated

Language: Английский

Citations

0
Role of trigger receptor 2 expressed on myeloid cells in neuroinflammation－neglected multidimensional regulation of microglia DOI
Xin Zhang, Xue Chen, Ling Zhang

et al.

Neurochemistry International, Journal Year: 2023, Volume and Issue: 171, P. 105639 - 105639

Published: Nov. 3, 2023

Language: Английский

Citations

9
Comparing neoantigen cancer vaccines and immune checkpoint therapy unveils an effective vaccine and anti-TREM2 macrophage-targeting dual therapy DOI Creative Commons
Sunita Keshari, Alexander S. Shavkunov, Qi Miao

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(11), P. 114875 - 114875

Published: Oct. 23, 2024

Language: Английский

Citations

2
The cross-talk between macrophages and tumor cells as a target for cancer treatment DOI Creative Commons
Muhammad Aizaz,

Aakif Ullah Khan,

Faisal Khan

et al.

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

Published: Nov. 14, 2023

Macrophages represent an important component of the innate immune system. Under physiological conditions, macrophages, which are essential phagocytes, maintain a proinflammatory response and repair damaged tissue. However, these processes often impaired upon tumorigenesis, in tumor-associated macrophages (TAMs) protect support growth, proliferation, invasion tumor cells promote suppression antitumor immunity. TAM abundance is closely associated with poor outcome cancer, impediment chemotherapy effectiveness ultimately dismal therapy inferior overall survival. Thus, cross-talk between cancer TAMs target for checkpoint therapies metabolic interventions, spurring interest it as therapeutic vulnerability both hematological cancers solid tumors. Furthermore, targeting this has emerged promising strategy treatment antibody against CD47 protein, critical macrophage recognized “don’t eat me” signal, well other metabolism-focused strategies. Therapies constitute milestone advancement anticancer research have had effects on not only phagocytosis activation but also adaptive system activation, effectively counteracting cells’ evasion shown context myeloid cancers. Targeting signaling one several possibilities to reverse immunosuppressive tumor-protective environment aim enhancing response. Several preclinical studies identified pathways that regulate recruitment, polarization, or metabolism TAMs. In review, we summarize current understanding role progression mechanisms by they communicate cells. Additionally, dissect various strategies developed macrophage–tumor cell cross-talk, including modulation blockade pathways, disruption physical interactions leukemia macrophages. Finally, highlight challenges hypoxia acidosis barriers effective discuss opportunities future field.

Language: Английский

Citations

4