Genetic variation in IL-4 activated tissue resident macrophages determines strain-specific synergistic responses to LPS epigenetically DOI Creative Commons
mingming zhao, Dragana Janković, Verena M. Link

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 25, 2025

Abstract How macrophages in the tissue environment integrate multiple stimuli depends on genetic background of host, but this is still poorly understood. We investigate IL-4 activation male C57BL/6 and BALB/c strain specific vivo tissue-resident (TRMs) from peritoneal cavity. TRMs are more transcriptionally responsive to stimulation, with induced genes associated super enhancers, topologically associating domains (TAD) boundaries. IL-4-directed epigenomic remodeling reveals enrichment NF-κB, IRF, STAT motifs. Additionally, IL-4-activated demonstrate an augmented synergistic response upon vitro lipopolysaccharide (LPS) exposure, despite naïve displaying a robust transcriptional LPS. Single-cell RNA sequencing (scRNA-seq) analysis mixed bone marrow chimeras indicates that differences synergy cell intrinsic within same environment. Hence, variation alters IL-4-induced epigenetic reprogramming resulting responses LPS exposure.

Language: Английский

GLUT3 promotes macrophage signaling and function via RAS-mediated endocytosis in atopic dermatitis and wound healing DOI Creative Commons

Dong-Min Yu,

Jiawei Zhao,

Eunice E. Lee

et al.

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(21)

Published: Sept. 18, 2023

The facilitative GLUT1 and GLUT3 hexose transporters are expressed abundantly in macrophages, but whether they have distinct functions remains unclear. We confirmed that expression increased after M1 polarization stimuli found M2 stimulation macrophages. Conditional deletion of Glut3 (LysM-Cre Glut3fl/fl) impaired bone marrow-derived Alternatively activated macrophages from the skin patients with atopic dermatitis showed expression, a calcipotriol-induced model was rescued LysM-Cre Glut3fl/fl mice. M2-like human wound tissues as assessed by transcriptomics costaining, significantly decreased nonhealing, compared healing, diabetic foot ulcers. In an excisional healing model, mice macrophage delayed healing. promoted IL-4/STAT6 signaling, independently its glucose transport activity. Unlike plasma membrane-localized GLUT1, localized primarily to endosomes required for efficient endocytosis IL-4Rα subunits. interacted directly GTP-bound RAS vitro vivo through intracytoplasmic loop domain, this interaction STAT6 activation polarization. PAK macropinocytosis were also without GLUT3, suggesting broader roles regulation endocytosis. Thus, is alternative function, transport-independent, RAS-mediated role activation.

Language: Английский

Citations

15
Mechanism of regulating macrophages/osteoclasts in attenuating wear particle-induced aseptic osteolysis DOI Creative Commons
Zhaoyang Yin,

Ge Gong,

Xinhui Liu

et al.

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

Published: Oct. 4, 2023

Joint replacement surgery is the most effective treatment for end-stage arthritis. Aseptic loosening caused by periprosthetic osteolysis a common complication after joint replacement. Inflammation induced wear particles derived from prosthetic biomaterials major cause of osteolysis. We emphasize that bone marrow-derived macrophages and their fusion-derived osteoclasts play key role in this pathological process. Researchers have developed multiple intervention approaches to regulate macrophage/osteoclast activation. Aiming at particle-induced aseptic osteolysis, review separately discusses molecular mechanism regulation ROS formation inflammatory response through RANKL-MAPKs-NF-κB pathway. These mechanisms osteoclast activation different ways, but they are not isolated each other. There also lot crosstalk among mechanisms. In addition, other diseases related briefly introduced. Therefore, we discuss these new findings context existing work with view developing strategies particle-associated based on macrophages/osteoclasts.

Language: Английский

Citations

15
Tumour-associated macrophages: versatile players in the tumour microenvironment DOI Creative Commons
Zoey Zeyuan Ji, Max Kam‐Kwan Chan, Alex Siu Wing Chan

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Oct. 26, 2023

Tumour-Associated Macrophages (TAMs) are one of the pivotal components tumour microenvironment. Their roles in cancer immunity complicated, both pro-tumour and anti-cancer activities reported, including not only angiogenesis, extracellular matrix remodeling, immunosuppression, drug resistance but also phagocytosis regression. Interestingly, TAMs highly dynamic versatile solid tumours. They show or activities, interplay between microenvironment stem cells under specific conditions. In addition to classic M1/M2 phenotypes, a number novel dedifferentiation phenomena discovered due advanced single-cell technology, e.g., macrophage-myofibroblast transition (MMT) macrophage-neuron (MNT). More importantly, emerging information demonstrated potential on immunotherapy, suggesting by therapeutic efficiency checkpoint inhibitors chimeric antigen receptor engineered based macrophages. Here, we summarized latest discoveries from basic translational research discussed their clinical relevance for cancers.

Language: Английский

Citations

11
Controllable Adaptive Molybdate‐Oligosaccharide Nanoparticles Regulate M2 Macrophage Mitochondrial Function and Promote Angiogenesis via PI3K/HIF‐1α/VEGF Pathway to Accelerate Diabetic Wound Healing DOI
Xiuhong Huang, Liqin Zheng,

Yueshan Zhou

et al.

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 13(3)

Published: Nov. 3, 2023

Abstract The complex wound environment of diabetic wounds leads to poor treatment efficacy, and the inflammatory disorders vascular injury are primary causes death in such patients. Herein, a sprayable, controllable adaptive, pH‐responsive nanosystem molybdate oligosaccharide (CMO) is specially developed as an immunomodulatory angiogenesis‐promotion material for healing. CMO exhibited release Mo 2+ (COS), specifically response alkalescent observed wounds. provide anti‐inflammatory by promoting M2 polarization through significantly stimulating macrophage mitochondrial function. Specifically, with certain concentration reduce reactive oxygen species (ROS) tumor necrosis factor α (TNF‐α) expression, upregulated membrane potential (MMP), superoxide dismutase (SOD), interleukin 10 (IL‐10) expression macrophages. Moreover, facilitate angiogenesis via upregulating PI3K/HIF‐1α/VEGF pathway—a critical process formation new blood vessels that supply nutrients healing tissue. Remarkably, promote cell viability migration endothelial cells, enhance angiogenic genes. In vitro vivo studies suggest this simple but powerful targeting function has become effective

Language: Английский

Citations

11
TMEM205 induces TAM/M2 polarization to promote cisplatin resistance in gastric cancer DOI Creative Commons
Qiang Fu,

Xuwei Wu,

Zhongqi Lu

et al.

Gastric Cancer, Journal Year: 2024, Volume and Issue: 27(5), P. 998 - 1015

Published: June 8, 2024

Abstract Cisplatin (DDP) is a basic chemotherapy drug for gastric cancer (GC). With the increase of DDP concentration in clinical treatment, cells gradually became resistant. Therefore, it necessary to find effective therapeutic targets enhance sensitivity GC DDP. Studies have shown that Transmembrane protein 205 (TMEM205) overexpressed DDP-resistant human epidermoid carcinoma and correlates with resistance, database analyses show TMEM also GC, but its role cisplatin-resistant remains unclear. In this study, we chose variety experiments vivo vitro, aiming investigate cisplatin resistance cancer. The results showed promoted proliferation, stemness, epithelial–mesenchymal transition (EMT), migration angiogenesis through activation Wnt/β-catenin signaling pathway. addition, TMEM205 promotes progression by inducing M2 polarization tumor-associated macrophages (TAMs). These suggest may be an target regulate DDP, providing new direction treatment.

Language: Английский

Citations

4
High glucose inhibits autophagy and promotes the proliferation and metastasis of colorectal cancer through the PI3K/AKT/mTOR pathway DOI Creative Commons
Feng Li,

Xing Wan,

Zhigui Li

et al.

Cancer Medicine, Journal Year: 2024, Volume and Issue: 13(11)

Published: June 1, 2024

Colorectal cancer (CRC) ranks among the most prevalent malignancies worldwide, characterized by its complex etiology and slow research progress. Diabetes, as an independent risk factor for CRC, has been widely certified. Consequently, this study centers on elucidating intricacies of CRC cells initiation progression within a high-glucose environment.

Language: Английский

Citations

4
Disruption of glucose homeostasis by bacterial infection orchestrates host innate immunity through NAD+/NADH balance DOI Creative Commons

Jingjing Tang,

Xiao Wang, Shukun Chen

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(9), P. 114648 - 114648

Published: Aug. 20, 2024

Metabolic reprogramming is crucial for activating innate immunity in macrophages, and the accumulation of immunometabolites essential effective defense against infection. The NAD

Language: Английский

Citations

4
IDH2 regulates macrophage polarization and tumorigenesis by modulating mitochondrial metabolism in macrophages DOI Creative Commons

Sung Woo Lee,

So Yoon Kim, Bokyung Kim

et al.

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: Sept. 10, 2024

Language: Английский

Citations

4
3D‐Printed Microfluidic‐Based Cell Culture System With Analysis to Investigate Macrophage Activation DOI Open Access
Major A. Selemani,

Giraso Keza Monia Kabandana,

Chengpeng Chen

et al.

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

Published: Feb. 18, 2025

ABSTRACT In this paper, we describe the development of 3D‐printed microfluidic cell culture devices that can be coupled with a circulation system to study dynamics both intracellular and extracellular (release) processes. Key approach is ability quantitate key analytes on minutes timescale either on‐line (in study, quantitating nitric oxide production using an amperometric flow cell) or off‐line work, itaconate LC/MS) analytical measurements. To demonstrate usefulness approach, chose macrophage polarization as function matrix (silk) fiber size, major area research in tissue engineering. It was found use larger fibers (1280 nm vs. smaller 512 fibers) led increases itaconate. These findings set foundation for future creation finely tuned 3D approaches areas where play significant role barrier transport integrated analysis markers needed.

Language: Английский

Citations

0
Preclinical study of engineering MSCs promoting diabetic wound healing and other inflammatory diseases through M2 polarization DOI Creative Commons
Di Wu,

Rencun Liu,

Xiaotong Cen

et al.

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 5, 2025

Diabetic foot ulcer (DFU) represents a common and severe complication of diabetes mellitus. Effective safe treatments need to be developed. Mesenchymal stem cells (MSCs) have demonstrated crucial roles in tissue regeneration, wound repair inflammation regulation. However, the function is limited. The safety efficacy gene-modified MSCs unknown. Therefore, this study aimed investigate whether genetically modified with highly efficient expression anti-inflammatory factors promote diabetic by regulating macrophage phenotype transition. This may provide new approach treating healing. In study, human umbilical cord-derived (hUMSCs) were using recombinant lentiviral vectors simultaneously overexpress three factors, interleukin (IL)-4, IL-10, IL-13 (MSCs-3IL). Cell counting kit-8, flow cytometry differentiation assay used detect criteria MSCs. Overexpression efficiency was evaluated cytometry, quantitative real-time PCR, Western blot, enzyme-linked immunosorbent assay, cell scratch assay. We also assessed MSCs-3IL's ability modulate Raw264.7 PCR. addition, we healing through rate calculation, HE staining, Masson immunohistochemical analysis PCNA, F4/80, CD31, CD86, CD206, IL-4, IL-10 IL-13. MSCs-3IL effect on several other models inflammation. efficiently expressed high levels IL-4 (mRNA transcription increased 15,000-fold 800,000-fold, protein secretion 400 200 ng/mL), 950,000-fold, 6 ng/mL). effectively induced phenotypic polarization pro-inflammatory M1-like macrophages (M1) towards M2-like (M2). enhancement does not change phenotype. dynamic distribution vivo normal no karyotype variation tumor risk observed. mouse model, promoted closure exceeding 96% after 14 days treatment. process aided altering (reduced CD86 CD206 expression) accelerating re-epithelialization. summary, our demonstrates that hUMSCs overexpressed key (IL-4, IL-13). MSCs-3IL-based therapy enhances safety. suggests could as novel therapeutic for DFU repair.

Language: Английский

Citations

0