Regulating the Polarization of Macrophages: A Promising Approach to Vascular Dermatosis

Peng, Huiling; Xian, Dehai; Liu, Jiexiong; Pan, Shihong; Tang, Ran; Zhong, Jianqiao

doi:10.1155/2020/8148272

Cited by 24 publications

(17 citation statements)

References 135 publications

(148 reference statements)

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“…The innate immune defense system plays a key protective role in the growth of infants and young children ( Yu et al, 2018 ). As expected, innate immunity is widespread in IH ( Ritter et al, 2006 ; Peng et al, 2020 ). Promoting cell cycle arrest and apoptosis are the main mechanisms of action of drugs for the treatment of IH ( Chen et al, 2019 ).…”

Section: Discussionsupporting

confidence: 75%

Integrated WGCNA and PPI Network to Screen Hub Genes Signatures for Infantile Hemangioma

Ouyang

et al. 2021

Front. Genet.

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BackgroundInfantile hemangioma (IH) is characterized by proliferation and regression.MethodsBased on the GSE127487 dataset, the differentially expressed genes (DEGs) between 6, 12, or 24 months and normal samples were screened, respectively. STEM software was used to screen the continued up-regulated or down-regulated in common genes. The modules were assessed by weighted gene co-expression network analysis (WGCNA). The enrichment analysis was performed to identified the biological function of important module genes. The area under curve (AUC) value and protein-protein interaction (PPI) network were used to identify hub genes. The differential expression of hub genes in IH and normal tissues was detected by qPCR.ResultsThere were 5,785, 4,712, and 2,149 DEGs between 6, 12, and 24 months and normal tissues. We found 1,218 DEGs were up-regulated or down-regulated expression simultaneously in common genes. They were identified as 10 co-expression modules. Module 3 and module 4 were positively or negatively correlated with the development of IH, respectively. These two module genes were significantly involved in immunity, cell cycle arrest and mTOR signaling pathway. The two module genes with AUC greater than 0.8 at different stages of IH were put into PPI network, and five genes with the highest degree were identified as hub genes. The differential expression of these genes was also verified by qRTPCR.ConclusionFive hub genes may distinguish for proliferative and regressive IH lesions. The WGCNA and PPI network analyses may help to clarify the molecular mechanism of IH at different stages.

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Section: Discussionsupporting

confidence: 75%

Integrated WGCNA and PPI Network to Screen Hub Genes Signatures for Infantile Hemangioma

Ouyang

et al. 2021

Front. Genet.

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“…The current research found a positive correlation between M1 and M2, which is contradictory to some previous literature, which is quite variable. Some studies found negative correlation between M1 and M2 by showing that the promotion of M2 macrophage polarization could suppress the M1 macrophage polarization, and vice versa, the inhibition of M2 macrophage polarization could promote the M1 macrophage polarization ( Abdelaziz et al, 2020 ; Peng et al, 2020 ). However, a previous study regarding breast cancer found a weak correlation between M1 and M2 macrophage densities in central tumor tissue of breast cancer ( Schnellhardt et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Molecular Subtypes of Oral Squamous Cell Carcinoma Based on Immunosuppression Genes Using a Deep Learning Approach

Mai

et al. 2021

Front. Cell Dev. Biol.

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Background: The mechanisms through which immunosuppressed patients bear increased risk and worse survival in oral squamous cell carcinoma (OSCC) are unclear. Here, we used deep learning to investigate the genetic mechanisms underlying immunosuppression in the survival of OSCC patients, especially from the aspect of various survival-related subtypes.Materials and methods: OSCC samples data were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and OSCC-related genetic datasets with survival data in the National Center for Biotechnology Information (NCBI). Immunosuppression genes (ISGs) were obtained from the HisgAtlas and DisGeNET databases. Survival analyses were performed to identify the ISGs with significant prognostic values in OSCC. A deep learning (DL)-based model was established for robustly differentiating the survival subpopulations of OSCC samples. In order to understand the characteristics of the different survival-risk subtypes of OSCC samples, differential expression analysis and functional enrichment analysis were performed.Results: A total of 317 OSCC samples were divided into one inferring cohort (TCGA) and four confirmation cohorts (ICGC set, GSE41613, GSE42743, and GSE75538). Eleven ISGs (i.e., BGLAP, CALCA, CTLA4, CXCL8, FGFR3, HPRT1, IL22, ORMDL3, TLR3, SPHK1, and INHBB) showed prognostic value in OSCC. The DL-based model provided two optimal subgroups of TCGA-OSCC samples with significant differences (p = 4.91E-22) and good model fitness [concordance index (C-index) = 0.77]. The DL model was validated by using four external confirmation cohorts: ICGC cohort (n = 40, C-index = 0.39), GSE41613 dataset (n = 97, C-index = 0.86), GSE42743 dataset (n = 71, C-index = 0.87), and GSE75538 dataset (n = 14, C-index = 0.48). Importantly, subtype Sub1 demonstrated a lower probability of survival and thus a more aggressive nature compared with subtype Sub2. ISGs in subtype Sub1 were enriched in the tumor-infiltrating immune cells-related pathways and cancer progression-related pathways, while those in subtype Sub2 were enriched in the metabolism-related pathways.Conclusion: The two survival subtypes of OSCC identified by deep learning can benefit clinical practitioners to divide immunocompromised patients with oral cancer into two subpopulations and give them target drugs and thus might be helpful for improving the survival of these patients and providing novel therapeutic strategies in the precision medicine area.

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“…In many cancers, tumor associated macrophages (TAM) acquire an M2-like fate that promotes metastasis by enhancing angiogenesis and ECM remodeling ( 56 , 57 ). Given the strong correlation between the macrophage fate acquisition and the disease progression, there is increasing focus on understanding the critical mediators that drive macrophage polarization states in order to develop targets for therapeutic interventions ( 58 ). For example, COX2 is required for the polarization of macrophages to an M2 state and several studies have reported that blocking the COX2 mediated inflammation using celecoxib treatment improves disease prognosis in the diseases discussed ( 59 , 60 ).…”

Section: Discussionmentioning

confidence: 99%

Epithelial-Macrophage Crosstalk Initiates Sterile Inflammation in Embryonic Skin

et al. 2021

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Macrophages are highly responsive to the environmental cues and are the primary responders to tissue stress and damage. While much is known about the role of macrophages during inflammatory disease progression; the initial series of events that set up the inflammation remains less understood. In this study, we use next generation sequencing (NGS) of embryonic skin macrophages and the niche cells - skin epithelia and stroma in the epidermis specific knockout of integrin beta 1 (Itgβ1) model to uncover specific roles of each cell type and identify how these cell types communicate to initiate the sterile inflammatory response. We demonstrate that while the embryonic skin fibroblasts in the Itgβ1 knockout skin are relatively inactive, the keratinocytes and macrophages are the critical responders to the sterile inflammatory cues. The epidermis expresses damage associated molecular patterns (DAMPs), stress response genes, pro-inflammatory cytokines, and chemokines that aid in eliciting the inflammatory response. The macrophages, in-turn, respond by acquiring enhanced M2-like characteristics expressing ECM remodeling and matrisome signatures that exacerbate the basement membrane disruption. Depletion of macrophages by blocking the CSF1 receptor (CSF1R) results in improved basement membrane integrity and reduced ECM remodeling activity in the KO skin. Further, blocking the skin inflammation with celecoxib reveals that the acquired fate of macrophages in the KO skin is dependent on its interaction with the epidermal compartment through COX2 dependent cytokine production. Taken together, our study highlights a critical crosstalk between the epithelia and the dermal macrophages that shapes macrophage fate and initiates sterile inflammation in the skin. The insights gained from our study can be extrapolated to other inflammatory disorders to understand the early events that set up the disease.

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Regulating the Polarization of Macrophages: A Promising Approach to Vascular Dermatosis

Cited by 24 publications

References 135 publications

Integrated WGCNA and PPI Network to Screen Hub Genes Signatures for Infantile Hemangioma

Integrated WGCNA and PPI Network to Screen Hub Genes Signatures for Infantile Hemangioma

Molecular Subtypes of Oral Squamous Cell Carcinoma Based on Immunosuppression Genes Using a Deep Learning Approach

Epithelial-Macrophage Crosstalk Initiates Sterile Inflammation in Embryonic Skin

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