Overexpression of S100A9 in obesity impairs macrophage differentiation via TLR4-NFkB-signaling worsening inflammation and wound healing

Franz, Sandra; Ertel, Anastasia; Engel, Kathrin M.; Simon, Jan C.; Saalbach, Anja

doi:10.7150/thno.67174

Cited by 41 publications

(26 citation statements)

References 77 publications

(113 reference statements)

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“…TNF-α and IL-6, which are potential targets of naringenin shown in Fig. 2d, are proinflammatory cytokines with increased expression in the wound microenvironment 84 .…”

Section: Molecular Dockingmentioning

confidence: 98%

Integrated network pharmacology and experimental validation to explore the mechanisms underlying naringenin treatment of chronic wounds

Sun

Liu

et al. 2023

Sci Rep

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Naringenin is a citrus flavonoid with various biological functions and a potential therapeutic agent for skin diseases, such as UV radiation and atopic dermatitis. The present study investigates the therapeutic effect and pharmacological mechanism of naringenin on chronic wounds. Using network pharmacology, we identified 163 potential targets and 12 key targets of naringenin. Oxidative stress was confirmed to be the main biological process modulated by naringenin. The transcription factor p65 (RELA), alpha serine/threonine-protein kinase (AKT1), mitogen-activated protein kinase 1 (MAPK1) and mitogen-activated protein kinase 3 (MAPK3) were identified as common targets of multiple pathways involved in treating chronic wounds. Molecular docking verified that these four targets stably bound naringenin. Naringenin promoted wound healing in mice in vivo by inhibiting wound inflammation. Furthermore, in vitro experiments showed that a low naringenin concentration did not significantly affect normal skin cell viability and cell apoptosis; a high naringenin concentration was cytotoxic and reduced cell survival by promoting apoptosis. Meanwhile, comprehensive network pharmacology, molecular docking and in vivo and in vitro experiments revealed that naringenin could treat chronic wounds by alleviating oxidative stress and reducing the inflammatory response. The underlying mechanism of naringenin in chronic wound therapy involved modulating the RELA, AKT1 and MAPK1/3 signalling pathways to inhibit ROS production and inflammatory cytokine expression.

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“…TNF-α and IL-6, which are potential targets of naringenin shown in Fig. 2d, are proinflammatory cytokines with increased expression in the wound microenvironment 84 .…”

Section: Molecular Dockingmentioning

confidence: 98%

Integrated network pharmacology and experimental validation to explore the mechanisms underlying naringenin treatment of chronic wounds

Sun

Liu

et al. 2023

Sci Rep

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“…These genes work together to allow the wound-healing process to proceed steadily and without overgrowth in healthy individuals. And in KPI with abnormal expression of RBP, overexpression of S100A9 has a proinflammatory effect and damages macrophage differentiation, and may even expand skin inflammation and delay skin repair ( Franz et al, 2022 ). HspB1 may increase the number of small fibers in mice and cause delayed muscle growth ( Kammoun et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Genome-wide analysis of dysregulated RNA-binding proteins and alternative splicing genes in keloid

Zhang

et al. 2023

Front. Genet.

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Introduction: The pathogenesis of keloids remains unclear.Methods: In this study, we analyzed RNA-Seq data (GSE113619) of the local skin tissue of 8 keloid-prone individuals (KPI) and 6 healthy controls (HC) before and 42 days after trauma from the gene expression omnibus (GEO) database. The differential alternative splicing (AS) events associated with trauma healing between KPIs and HCs were identifified, and their functional differences were analyzed by gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathways. The co-expression relationship of differentially alternative splicing genes and differentially expressed RNA binding proteins (RBPs) was established subsequently.Results: A total of 674 differential AS events between the KD42 and the KD0 and 378 differential AS events between the HD42 and the HD0 were discovered. Notably, most of the differential genes related to keloids are enriched in actin, microtubule cells, and cortical actin cytoskeletal tissue pathway. We observed a signifificant association between AS genes (EPB41, TPM1, NF2, PARD3) and trauma healing in KPIs and HCs. We also found that the differential expression of healthy controls-specifific trauma healing-related RBPs (TKT, FDPS, SAMHD1) may affect the response of HCs to trauma healing by regulating the AS of downstream trauma healing-related genes such as DCN and DST. In contrast, KPIs also has specifific differential expression of trauma healing related RBPs (S100A9, HspB1, LIMA1, FBL), which may affect the healing response of KPIs to trauma by regulating the AS of downstream trauma healing-related genes such as FN1 and TPM1.Discussion: Our results were innovative in revealing early wound healing-related genes (EPB41, TPM1, NF2, PARD3) in KPI from the perspective of AS regulated by RBPs.

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“…attenuates the development of M2 and induces pro-in ammatory functions in obesity [37]. Under hyperglycemic conditions, the upregulation of S100A9 induces an activating histone code on the gene promoter in M1 macrophages [38].…”

Section: Discussionmentioning

confidence: 99%

S100A9 Regulated M1/M2 Macrophage Polarization in Interleukin-10- induced Promotion of Malignant Pleural Effusion

Pei¹,

Yi²,

Dong³

et al. 2023

Preprint

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Interlukin-10 (IL-10) promotes the formation and development of malignant pleural effusion (MPE). Previous studies have elucidated the pathogenesis from the view of the immune-regulation function of CD4+ T-cells. However, the underlying mechanism is still not fully understood. In this study, our results showed that IL-10 deficiency reduced the percentage of macrophages in mouse MPE and regulated M1/M2 polarization in vivo and in vitro. The migration capacity of tumor cells was suppressed, and apoptosis was promoted when tumor cells were co-cultured with MPE macrophages in the absence of IL-10. Messenger RNA sequencing of MPE macrophages showed that S100A9 was downregulated in IL-10−/− mice. Bone marrow–derived macrophages obtained from wild-type mice transfected with S100A9-specific small interfering RNAs (siRNAs) also showed less M2 and more M1 polarization than those from the siRNA control group. Furthermore, downregulation of S100A9 using S100A9-specific siRNA suppressed MPE development, decreased macrophages, and modulated macrophage polarization in MPE in vivo. In conclusion, S100A9 plays a vital role in the process of IL-10 deficiency–mediated MPE suppression by regulating M1/M2 polarization, thus influencing the tumor-migration capacity and apoptosis. This could result in clinically applicable strategies to inhibit the formation of MPE by regulating the polarization of MPE macrophages.

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Overexpression of S100A9 in obesity impairs macrophage differentiation via TLR4-NFkB-signaling worsening inflammation and wound healing

Cited by 41 publications

References 77 publications

Integrated network pharmacology and experimental validation to explore the mechanisms underlying naringenin treatment of chronic wounds

Integrated network pharmacology and experimental validation to explore the mechanisms underlying naringenin treatment of chronic wounds

Genome-wide analysis of dysregulated RNA-binding proteins and alternative splicing genes in keloid

S100A9 Regulated M1/M2 Macrophage Polarization in Interleukin-10- induced Promotion of Malignant Pleural Effusion

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