Targeting macrophage autophagy for inflammation resolution and tissue repair in inflammatory bowel disease

Wang, Er-jin; Wu, Mingyue; Ren, Zheng-yu; Zheng, Ying; Ye, Richard D.; Tan, Chris Soon Heng; Wang, Ying; Lu, Jiahong

doi:10.1093/burnst/tkad004

Cited by 14 publications

(5 citation statements)

References 134 publications

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“…It highlights the interactions between proteins regulating macrophage polarization and macrophage autophagy in atherosclerosis ( 21 ). Specifically, the proteins colored in green regulate macrophage polarization, and the proteins highlighted in red are constituents of the NF-κB complex, which regulates inflammatory responses ( 116 ), autophagy, and macrophage autophagy ( 117 ). IL18 and TRAF6 nodes in the macrophage autophagy network regulate inflammatory processes and plaque instability in atherosclerosis ( 118 , 119 ).…”

Section: Resultsmentioning

confidence: 99%

Effects of vitamin D signaling in cardiovascular disease: centrality of macrophage polarization

Fliri,

Kajiji

2024

Front. Cardiovasc. Med.

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Among the leading causes of natural death are cardiovascular diseases, cancer, and respiratory diseases. Factors causing illness include genetic predisposition, aging, stress, chronic inflammation, environmental factors, declining autophagy, and endocrine abnormalities including insufficient vitamin D levels. Inconclusive clinical outcomes of vitamin D supplements in cardiovascular diseases demonstrate the need to identify cause-effect relationships without bias. We employed a spectral clustering methodology capable of analyzing large diverse datasets for examining the role of vitamin D's genomic and non-genomic signaling in disease in this study. The results of this investigation showed the following: (1) vitamin D regulates multiple reciprocal feedback loops including p53, macrophage autophagy, nitric oxide, and redox-signaling; (2) these regulatory schemes are involved in over 2,000 diseases. Furthermore, the balance between genomic and non-genomic signaling by vitamin D affects autophagy regulation of macrophage polarization in tissue homeostasis. These findings provide a deeper understanding of how interactions between genomic and non-genomic signaling affect vitamin D pharmacology and offer opportunities for increasing the efficacy of vitamin D-centered treatment of cardiovascular disease and healthy lifespans.

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Section: Resultsmentioning

confidence: 99%

Effects of vitamin D signaling in cardiovascular disease: centrality of macrophage polarization

Fliri,

Kajiji

2024

Front. Cardiovasc. Med.

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“…Beyond the aspect of cell respiration, in the result of potential connection between metabolic genes and phagocytotic functions, Lamp1, a member of lysosome-associated membrane glycoproteins involving in autophagy process ( 56 ), and Clec genes (Clec7a, Clec4d, and Clec4e), which belongs to C-type lectin receptors participating in pathogens clearance ( 57 ), stand out in our data. Autophagy is a pathway by which macrophages eliminate pathogens, and the autophagy flux is closely related with cellular metabolism ( 58 , 59 ). Arginine metabolism genes Arg1 and Odc1 and FAO genes Fabp7, which were all dominantly expressed in GM, positively correlated with Clec7a which highly expressed in GM ( Figure 6B ; Table S2 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated transcriptomic and metabolomic analysis reveals the metabolic programming of GM-CSF- and M-CSF- differentiated mouse macrophages

Zhang,

Song,

Liu

et al. 2023

Front. Immunol.

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Macrophages play a critical role in the inflammatory response and tumor development. Macrophages are primarily divided into pro-inflammatory M1-like and anti-inflammatory M2-like macrophages based on their activation status and functions. In vitro macrophage models could be derived from mouse bone marrow cells stimulated with two types of differentiation factors: GM-CSF (GM-BMDMs) and M-CSF (M-BMDMs), to represent M1- and M2-like macrophages, respectively. Since macrophage differentiation requires coordinated metabolic reprogramming and transcriptional rewiring in order to fulfill their distinct roles, we combined both transcriptome and metabolome analysis, coupled with experimental validation, to gain insight into the metabolic status of GM- and M-BMDMs. The data revealed higher levels of the tricarboxylic acid cycle (TCA cycle), oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and urea and ornithine production from arginine in GM-BMDMs, and a preference for glycolysis, fatty acid storage, bile acid metabolism, and citrulline and nitric oxide (NO) production from arginine in M-BMDMs. Correlation analysis with the proteomic data showed high consistency in the mRNA and protein levels of metabolic genes. Similar results were also obtained when compared to RNA-seq data of human monocyte derived macrophages from the GEO database. Furthermore, canonical macrophage functions such as inflammatory response and phagocytosis were tightly associated with the representative metabolic pathways. In the current study, we identified the core metabolites, metabolic genes, and functional terms of the two distinct mouse macrophage populations. We also distinguished the metabolic influences of the differentiation factors GM-CSF and M-CSF, and wish to provide valuable information for in vitro macrophage studies.

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“… 309 , 311 Upon activation, M1 macrophages rapidly produce and secrete various proinflammatory cytokines and chemokines, including IL‐1β, IL‐6, IL‐12, IL‐23, and TNF‐α. 22 , 312 , 313 These mediators orchestrate the inflammatory response, recruiting additional immune cells to the injury site and amplifying the inflammatory cascade.…”

Section: Macrophages: Orchestrators Of Tissue Repair and Regenerationmentioning

confidence: 99%

Macrophage plasticity: signaling pathways, tissue repair, and regeneration

Yan,

Wang,

Cai

et al. 2024

MedComm

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Macrophages are versatile immune cells with remarkable plasticity, enabling them to adapt to diverse tissue microenvironments and perform various functions. Traditionally categorized into classically activated (M1) and alternatively activated (M2) phenotypes, recent advances have revealed a spectrum of macrophage activation states that extend beyond this dichotomy. The complex interplay of signaling pathways, transcriptional regulators, and epigenetic modifications orchestrates macrophage polarization, allowing them to respond to various stimuli dynamically. Here, we provide a comprehensive overview of the signaling cascades governing macrophage plasticity, focusing on the roles of Toll‐like receptors, signal transducer and activator of transcription proteins, nuclear receptors, and microRNAs. We also discuss the emerging concepts of macrophage metabolic reprogramming and trained immunity, contributing to their functional adaptability. Macrophage plasticity plays a pivotal role in tissue repair and regeneration, with macrophages coordinating inflammation, angiogenesis, and matrix remodeling to restore tissue homeostasis. By harnessing the potential of macrophage plasticity, novel therapeutic strategies targeting macrophage polarization could be developed for various diseases, including chronic wounds, fibrotic disorders, and inflammatory conditions. Ultimately, a deeper understanding of the molecular mechanisms underpinning macrophage plasticity will pave the way for innovative regenerative medicine and tissue engineering approaches.

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Targeting macrophage autophagy for inflammation resolution and tissue repair in inflammatory bowel disease

Cited by 14 publications

References 134 publications

Effects of vitamin D signaling in cardiovascular disease: centrality of macrophage polarization

Effects of vitamin D signaling in cardiovascular disease: centrality of macrophage polarization

Integrated transcriptomic and metabolomic analysis reveals the metabolic programming of GM-CSF- and M-CSF- differentiated mouse macrophages

Macrophage plasticity: signaling pathways, tissue repair, and regeneration

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