WTAP Mediated N6-methyladenosine RNA Modification of ELF3 Drives Cellular Senescence by Upregulating IRF8

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(5), P. 1763 - 1777

Published: Jan. 1, 2024

N6-methyladenosine (m6A), the most prevalent posttranscriptional RNA modification, involved in various diseases and cellular processes.However, underlying mechanisms of m6A regulation skin aging are still not fully understood.In this study, proteomics analysis revealed a significant correlation between Wilms' tumor 1-associating protein (WTAP) expression senescence.Next, upregulated WTAP was detected tissues senescent human dermal fibroblasts (HDFs).Functionally, overexpressed induced senescence knockdown rescued HDFs.Mechanistically, directly targeted ELF3 promoted its an m6A-dependent manner.Exogenous-ELF3 overexpression evidently reversed shWTAP-suppressed fibroblast senescence.Furthermore, IRF8-mediated senescence-associated secretory phenotype (SASP) by binding to (-817 -804) site IRF8 promoter directly.In vivo, increased cells aging.In summary, these findings critical role WTAP-mediated modification identified as important target HDFs senescence, providing new idea for delaying process.

Language: Английский

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Quercetin attenuates inflammation in rosacea by directly targeting p65 and ICAM-1

Life Sciences, Journal Year: 2024, Volume and Issue: 347, P. 122675 - 122675

Published: April 28, 2024

Language: Английский

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High-sensitive sensory neurons exacerbate rosacea-like dermatitis in mice by activating γδ T cells directly

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 23, 2024

Rosacea patients show facial hypersensitivity to stimulus factors (such as heat and capsaicin); however, the underlying mechanism of this hyperresponsiveness remains poorly defined. Here, we capsaicin stimulation in mice induces exacerbated rosacea-like dermatitis but has no apparent effect on normal skin. Nociceptor ablation substantially reduces dermatitis. Subsequently, find that γδ T cells express Ramp1, receptor neuropeptide CGRP, are close contact with these nociceptors significantly increased rosacea skin lesions can be further recruited activated by neuron-secreted CGRP. Rosacea-like is reduced cell δ-deficient (Tcrd−/−) mice, nociceptor-mediated aggravation also mice. In vitro experiments CGRP IL17A secretion from regulating inflammation-related metabolism-related pathways. Finally, rimegepant, a antagonist, shows efficacy treatment conclusion, our findings demonstrate neuron-CGRP-γδT axis contributes rosacea, thereby showing targeting potentially effective therapeutic strategy for rosacea. common chronic inflammatory cutaneous disease pepper stimulation. Here authors use mouse model functions nociceptors, response involvement like-disease.

Language: Английский

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Signaling pathways and targeted therapy for rosacea

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 16, 2024

Rosacea is a chronic skin inflammatory disease with global prevalence ranging from 1% to 20%. It characterized by facial erythema, telangiectasia, papules, pustules, and ocular manifestations. Its pathogenesis involves complex interplay of genetic, environmental, immune, microbial, neurovascular factors. Recent studies have advanced our understanding its molecular basis, focusing on toll-like receptor (TLR) 2 pathways, LL37 expression, mammalian target rapamycin (mTOR) activation, interleukin (IL)-17 signaling, transient potential vanilloid (TRPV) functions, the Janus kinase-signal transducer activator transcription (JAK-STAT) pathways. LL37-associated signaling particularly involving TLR2 mTORC1, are critical in rosacea. interacts molecules such as extracellular signal-regulated kinases 1 (ERK1/2), nuclear factor kappa B (NF- κ B), inflammasomes, C-X-C motif chemokine ligand 8 (CXCL8), mas-related G-protein-coupled X2 (MRGPRX2)-TRPV4, vascular endothelial growth (VEGF). This interaction activates macrophages, neutrophils, mast cells, leading cytokine release including tumor necrosis factor-alpha (TNF- α ), IL-6, IL-1 β , C (CCL) 5, CXCL9, CXCL10. These processes contribute immune response modulation, inflammation, angiogenesis rosacea pathophysiology. The IL-17 pathway also plays crucial role rosacea, affecting production cytokines. In addition, recent insights into JAK/STAT pathways revealed their integral angiogenic mechanisms associated treatment currently focuses symptom management, emerging these providing more targeted effective therapies. Biological agents targeting specific cytokines, inhibitors, JAK VEGF antagonists promising for future therapy, aiming enhanced efficacy fewer side effects. review provides comprehensive overview current knowledge regarding therapeutic strategies.

Language: Английский

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Neurotransmitter 5-HT Further Promotes LL-37-Induced Rosacea-like Inflammation Through HTR3A

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3156 - 3156

Published: March 28, 2025

Rosacea is a chronic inflammatory skin disease and usually accompanied by extensive macrophage infiltration. There growing evidence suggesting that neurotransmitter 5-hydroxytryptamine (5-HT) plays crucial role in reactions. However, the interaction between 5-HT rosacea still unclear. Here, we hypothesized inflammation of partly caused 5-HT, investigated underlying mechanism. In this study, employed model induced LL-37, which applicated as stimulator, to investigate effects on vitro vivo. LL-37-(4 μM)-induced THP-1-derived macrophages, (400 μM) further promoted secretion cytokines polarized macrophages towards M1 phenotype, could promote an response. Further research revealed exposure LL-37 (L5) selectively upregulated HTR3A mRNA expression but not HTR2A or HTR7 colocalization with HTR3A. Notably, application antagonist tropisetron (TPS) siRNA suppressed L5-induced inflammation. Meanwhile, (25 μg each injection total three times) deteriorated erythema, stimulated dermal cell infiltration, (40 μL 320 μM four rosacea-like mice, while these undesirable were reversed using TPS. Our findings LL-37-induced through study highlights promising therapeutic target, warrants in-depth investigation into its clinical applicability.

Language: Английский

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Research Progress of Dihydroquercetin in the Treatment of Skin Diseases

Molecules, Journal Year: 2023, Volume and Issue: 28(19), P. 6989 - 6989

Published: Oct. 9, 2023

Skin is a barrier to maintaining the stability of human environment and preventing invasion pathogens. When skin tissue exposed external environment, it will inevitably develop defects due trauma, injury, burns, ulcers, surgery, chronic diseases. Rapid repair key reducing infection, relieving pain, improving quality life. Dihydroquercetin kind flavonoid that has wide range pharmacological activities can improve repair, inflammation, cancer, so on. In this paper, application dihydroquercetin in medical dressings research progress treatment skin-related diseases are reviewed, as provide reference for further developing drug

Language: Английский

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Unveiling the Mechanism of Liangxue Siwu Decoction in Treating Rosacea Through Network Pharmacology and in-vitro Experimental Validation

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 5685 - 5699

Published: Aug. 1, 2024

Rosacea, a recurring dermatological disorder, demands effective therapeutic approaches. Traditional Chinese medicine, particularly Liangxue Siwu Decoction (LXSWD), has shown promise in managing inflammatory skin diseases, such as rosacea. This study focuses on uncovering LXSWD's specific effects the symptoms of

Language: Английский

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Flushing New Light on Rosacea

Journal of Investigative Dermatology, Journal Year: 2023, Volume and Issue: 144(5), P. 934 - 935

Published: Dec. 15, 2023

Language: Английский

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