LCN2 Mediates Skin Inflammation in Psoriasis through the SREBP2‒NLRC4 Axis

Ma, Jingyi; Chen, Jiaoling; Xue, Ke; Chen, Yu; Dang, Erle; Qiao, Hongjiang; Fang, Hui; Pang, Bingyu; Li, Qingyang; Sun, Zhen; Qiao, Pei; Wang, Lei; Wang, Gang; Shao, Shuai

doi:10.1016/j.jid.2022.01.012

Cited by 20 publications

(12 citation statements)

References 34 publications

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“…We observed the differential genes of Ne.7 in the heatmap, found in IBDP was enriched in specific genes (Chil3, Saa3, Lcn2, Retnlg) associated with neutrophil activation(Appendix Fig. 4B) (Goren et al 2014;Ma et al 2022;Uyar et al 2022). Monocle analysis indicated that Ne.5 was in the (b) stage and Ne.7 was mainly focused in the (c) stage, which are both at the late stage of projected timeline trajectory, whereas the pseudo-time trajectory split into 2 main branches at opposite divergent ends as 2 terminally differentiated cell types.…”

Section: Prdx1 + Neutrophils Induce Oxidative Phosphorylation-aggrava...mentioning

confidence: 93%

Single-Cell Analyses of the Oral Mucosa Reveal Immune Cell Signatures

Liu

Jiang

et al. 2023

J Dent Res

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Inflammatory bowel disease (IBD) is a common immune-related disease of the gastrointestinal tract that affects many people around the world. Extraintestinal manifestations of IBD have been frequently observed in recent years; one of these, periodontitis, has gained increasing attention. Periodontitis is a chronic inflammatory disease characterized by inflammation and destruction of periodontal tissues due to the disruption of host immune homeostasis. Clinical studies have revealed that periodontal inflammation is associated with IBD. However, the detailed heterogeneity of immune cells and their developmental relationships remain poorly understood at the single-cell level. In this study, we performed single-cell RNA (scRNA) sequencing to assess the transcriptome heterogeneity in periodontal tissues. We found the cellular composition and subclusters with specific gene expression profiles by uniform manifold approximation and projection. Pseudo-time analysis combined with gene enrichment analysis was performed to reveal cell states and key pathways. Ligand–receptor pairs revealed cell–cell communication among the immune cell types in periodontal tissues. Based on our analysis, we identified an essential role for Tcr+ macrophage, Prdx1+ neutrophil, and Mif+ T subpopulations with proinflammatory phenotype infiltration. Moreover, we examined the heterogeneity of monocytic cells and B cells. Collectively, the mapping of scRNA revealed the complex cellular landscape of oral mucosa immune cells and highlighted these immune cells as a previously unrecognized factor that may aggravate inflammation. Our analysis proves that periodontitis could exacerbate colitis and provides novel ideas for controlling and preventing IBD exacerbations.

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Section: Prdx1 + Neutrophils Induce Oxidative Phosphorylation-aggrava...mentioning

confidence: 93%

Single-Cell Analyses of the Oral Mucosa Reveal Immune Cell Signatures

Liu

Jiang

et al. 2023

J Dent Res

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“…LCN2, which is a member of the Lipocalin superfamily, is a 25-kDa secreted protein that is expressed in a variety of cells and is involved in the transport of lipophilic small molecules such as steroids, lipopolysaccharides, iron, and fatty acids. Recent studies have suggested that LCN2 inhibits NLRC4 signaling through SREBP2 to alleviate psoriatic dermatitis ( Ma et al, 2022 ). Therefore, we measured the mRNA and protein expression of LCN2 in the different groups on the 10th day and found that the mRNA and protein expression were upregulated in IMQ-induced psoriasis-like skin lesions compared with those in the control group, whereas BZLF inhibited LCN2 mRNA and protein expression ( Figures 7A, B ).…”

Section: Resultsmentioning

confidence: 99%

Banzhilian formula alleviates psoriasis-like lesions via the LCN2/MMP-9 axis based on transcriptome analysis

Xing

Yan²,

Guo³

et al. 2023

Front. Pharmacol.

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Introduction: Oral Banzhilian formula (BZLF) is effective in the clinical treatment of psoriasis. However, the effectiveness and mechanism of different drug delivery routes deserve further study.Methods: First, we established the mouse model of psoriasis using imiquimod (IMQ), and high-performance liquid chromatography (HPLC) was used for the quality control of BZLF. Secondly, Total RNA Sequencing and bioinformatics analysis were used to explore the regulatory mechanism of BZLF in improving psoriatic lesions. Finally, further verification was based on animal experiments.Results: we externally applied BZLF for skin lesions in an imiquimod-induced psoriasis mouse model and found that BZLF alleviated psoriasis-like skin lesions while inhibiting the expression of Ki67 and inflammatory factors (Il17a, Tnf-α, S100a7 and Cxcl1) in skin lesions. Transcriptome sequencing results suggested that BZLF inhibited signalling pathways closely related to psoriatic inflammation, such as the IL-17 signalling pathway, chemokine signalling pathway, TNF signalling pathway, and NF-kappa B signalling pathway, and the protein-protein interaction (PPI) network identified LCN2 as one of the core target genes and screened out its regulated downstream gene MMP9.Discussion: Our findings suggest that the anti-psoriatic mechanism of BZLF involved in downregulating the LCN2/MMP-9 axis.

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“…Previous studies have also shown that NLRC4 is involved in tumor progression, including breast cancer and colitis-associated cancer [ 42 , 43 ]. Ma et al reported a critical role for the LCN2–SREBP2–NLRC4 axis in psoriasis pathogenesis [ 44 ]. But the role of NLRC4 in skin aging remains poorly characterized.…”

Section: Discussionmentioning

confidence: 99%

p16INK4a Plays Critical Role in Exacerbating Inflammaging in High Fat Diet Induced Skin

Liang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. Long term high fat diets (HFD) promote skin aging pathogenesis, but detailed mechanisms remain unclear especially for inflammaging, which has recently emerged as a pathway correlating aging and age-related disease with inflammation. p16INK4a (hereafter termed p16) inhibits the cell cycle, with p16 deletion significantly inhibiting inflammaging. We observed that HFD-induced p16 overexpression in the skin. Therefore, we investigated if p16 exacerbated inflammaging in HFD-induced skin and also if p16 deletion exerted protective effects against this process. Methods. Eight-week-old double knockout (KO) ApoE-/-p16-/- mice and ApoE-/- littermates were fed HFD for 12 weeks and their skin phenotypes were analyzed. We measured skin fibrosis, senescence-associated secretory phenotype (SASP) levels, and integrin-inflammasome pathway activation using histopathological, RNA-sequencing (RNA-seq), bioinformatics analysis, and molecular techniques. Results. We found that HFD contributed to inflammaging in the skin by activating the NLRP3 inflammasome pathway, increasing inflammatory infiltration, and promoting apoptosis by balancing expression between proapoptotic and antiapoptotic molecules. p16 knockout, when compared with the ApoE-/- phenotype, inhibited skin fibrosis by ameliorating inflammatory infiltration and proinflammatory factor expression (Interleukin-1β (IL-1β), Interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)), and also alleviated inflammaging skin progress induced by HFD in the ApoE-/- mouse model. RNA-seq showed that p16 KO mice inhibited both integrin-inflammasome and NF-κB proinflammatory pathway activation. Conclusions. p16 deletion or p16 positive cell clearance could be a novel strategy preventing long term HFD-induced skin aging.

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LCN2 Mediates Skin Inflammation in Psoriasis through the SREBP2‒NLRC4 Axis

Cited by 20 publications

References 34 publications

Single-Cell Analyses of the Oral Mucosa Reveal Immune Cell Signatures

Single-Cell Analyses of the Oral Mucosa Reveal Immune Cell Signatures

Banzhilian formula alleviates psoriasis-like lesions via the LCN2/MMP-9 axis based on transcriptome analysis

p16INK4a Plays Critical Role in Exacerbating Inflammaging in High Fat Diet Induced Skin

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