Cell death in skin function, inflammation, and disease

Biochemical Journal, Journal Year: 2022, Volume and Issue: 479(15), P. 1621 - 1651

Published: Aug. 5, 2022

Cell death is an essential process that plays a vital role in restoring and maintaining skin homeostasis. It supports recovery from acute injury infection regulates barrier function immunity. can also provoke inflammatory responses. Loss of cell membrane integrity with lytic forms incite inflammation due to the uncontrolled release contents. Excessive or poorly regulated increasingly recognised as contributing cutaneous inflammation. Therefore, drugs inhibit could be used therapeutically treat certain diseases. Programmes develop such inhibitors are already underway. In this review, we outline mechanisms skin-associated programmes; apoptosis, necroptosis, pyroptosis, NETosis, epidermal terminal differentiation programme, cornification. We discuss evidence for their disease therapeutic opportunities targeting machinery.

Language: Английский

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Ferroptosis contribute to neonicotinoid imidacloprid-evoked pyroptosis by activating the HMGB1-RAGE/TLR4-NF-κB signaling pathway

Ecotoxicology and Environmental Safety, Journal Year: 2023, Volume and Issue: 253, P. 114655 - 114655

Published: Feb. 20, 2023

Imidacloprid (IMI) is among the common neonicotinoid insecticides used in agriculture worldwide, posing a potential toxic threat to non-target animals and humans. Numerous studies have shown that ferroptosis involved pathophysiological progression of renal diseases. However, it remains unclear whether IMI-induced nephrotoxicity. In present study, we investigated pathogenic role kidney damage vivo. Transmission electron microscopy (TEM) showed mitochondrial crest cells significantly decreased following IMI exposure. Moreover, exposure triggered lipid peroxidation kidney. We confirmed nuclear factor erythroid 2-related 2 (Nrf2)-mediated antioxidant capability was negatively correlated with induced by Importantly, verified NOD-, LRR-, pyrin domain-containing protein 3 (NLRP3)-driven inflammation occurred kidneys exposure, but pretreatment inhibitor ferrostatin (Fer-1) blocked this phenomenon. Additionally, F4/80+ macrophages accumulated proximal tubules kidneys, also increased expression high-mobility group box 1 (HMGB1), receptor for advanced glycation end products (RAGE), (TLR4), kappa-B (NF-κB). contrast, inhibition Fer-1 NLRP3 inflammasome activation, F4/80 positive macrophages, HMGB1-RAGE/TLR4 signaling pathway. To best our knowledge, first study reveal stress can induce Nrf2 inactivation, thereby triggering ferroptosis, causing an initial wave death, activating signaling, which promotes pyroptosis perpetuates dysfunction.

Language: Английский

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ACSL4 inhibition prevents macrophage ferroptosis and alleviates fibrosis in bleomycin-induced systemic sclerosis model

Arthritis Research & Therapy, Journal Year: 2023, Volume and Issue: 25(1)

Published: Oct. 26, 2023

Systemic sclerosis (SSc), with unclear pathophysiology, is a paradigmatic rheumatic disease of immunity dysfunction-driven multi-organ inflammation and ultimate fibrosis. Pathogenesis breakthroughs are urgently needed for available treatments halting its unremitting stiffness. This study aims to investigate whether ferroptosis can regulate the progressive SSc fibrosis.In vivo, bleomycin (BLM)-induced mice model was subjected detection using western blotting, malondialdehyde (MDA), glutathione (GSH) assays. Pharmacological inhibitor acyl-CoA synthetase long-chain family member 4 (ACSL4) utilized explore potential therapeutic effects fibrosis, from histological, biochemical, molecular analyses. In vitro, bone marrow-derived macrophages (BMDM) were activated into inflammatory phenotype then relationship evaluated between activation level sensitivity in lipopolysaccharide (LPS) incubation gradient concentrations. The calpain/ACSL4 axis analyzed after calpain knockdown or over-expression Raw264.7.Both skin lung tissue present enhanced ACSL4 expression, while inhibition effectively halted fibrosis progressing provides protection milieu. Meanwhile, positive regulation LPS-induced macrophage activity be observed. After knockdown, both expression decreased, renders ACSL4-envoking condition. Also, pharmacological reduced aptitude mice.ACSL4 induces aggravate progressing. upregulators calpains may targets BLM SSc.

Language: Английский

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Ferroptosis Activation Contributes to the Formation of Skin Lesions in Psoriasis Vulgaris

Antioxidants, Journal Year: 2023, Volume and Issue: 12(2), P. 310 - 310

Published: Jan. 29, 2023

(1) Background: Ferroptosis is a newly coined form of programmed cell death marked by lethal accumulation lipid peroxidation and ferrous iron overload. A few studies on the specific mechanism ferroptosis in genesis development psoriasis are available. (2) Methods: Levels reactive oxygen species (ROS) were measured flow cytometry. Ultrastructure analysis was performed transmission electron microscopy. Imiquimod-induced psoriasis-like mice treated with inducer. The expressions mRNA genes qRT-PCR. HaCaT cells used to explore function Cyb561d2. (3) Results: In this work, we observed that levels ROS epidermis vulgaris (PV) patients increased. existence activation individuals PV confirmed microscope both models. Intradermal injection inducer RSL3 significantly promoted aggravated dermatitis, level serum transferrin also increased samples. Moreover, abnormal expression some related metabolism proved cases, among which Cyb561d2 shown promote overload cells. (4) Conclusions: summary, our study suggested owing may be novel underlying formation skin lesions PV.

Language: Английский

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Neutrophils extracellular traps and ferroptosis in diabetic wounds

International Wound Journal, Journal Year: 2023, Volume and Issue: 20(9), P. 3840 - 3854

Published: May 17, 2023

Abstract Wound healing is an extremely complex process involving multiple levels of cells and tissues. It mainly completed through four stages: haemostasis, inflammation, proliferation, remodelling. When any one these stages impaired, it may lead to delayed or even transformation into chronic refractory wounds. Diabetes a kind common metabolic disease that affects approximately 500 million people worldwide, 25% whom develop skin ulcers break down repeatedly are difficult heal, making growing public health problem. Neutrophils extracellular traps ferroptosis new types programmed cell death identified in recent years have been found interact with diabetic In this paper, the normal wound interfering factors were outlined. The mechanism two kinds was also described, interaction between different wounds discussed.

Language: Английский

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