Altered expression of ferroptosis markers and iron metabolism reveals a potential role of ferroptosis in vitiligo

Wu, Xi; Jin, Shanglin; Yang, Yiwen; Lu, Xiaoli; Dai, Xiaoxi; Xu, Zhongyi; Zhang, Cheng‐Feng; Xiang, Leihong

doi:10.1111/pcmr.13032

Cited by 19 publications

(15 citation statements)

References 36 publications

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“…Epidermal melanocytes of patients with vitiligo have a remarkable features of pro-pyroptosis and proferroptosis. A recent report has shown that ferroptosis is involved in the pathogenesis of melanocyte destruction in vitiligo [73], which was consistent with our results, and confirmed the reliability of our analysis methods. Some researchers have made an assumption without direct evidence that pyroptosis is involved in the pathogenesis of melanocyte destruction [74].…”

Section: Discussionsupporting

confidence: 93%

Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level

Zhang

et al. 2022

J Transl Med

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Background Approximately 8–9% of the world’s population is affected by autoimmune diseases, and yet the mechanism of autoimmunity trigger is largely understudied. Two unique cell death modalities, ferroptosis and pyroptosis, provide a new perspective on the mechanisms leading to autoimmune diseases, and development of new treatment strategies. Methods Using scRNA-seq datasets, the aberrant trend of ferroptosis and pyroptosis-related genes were analyzed in several representative autoimmune diseases (psoriasis, atopic dermatitis, vitiligo, multiple sclerosis, systemic sclerosis-associated interstitial lung disease, Crohn’s disease, and experimental autoimmune orchitis). Cell line models were also assessed using bulk RNA-seq and qPCR. Results A substantial difference was observed between normal and autoimmune disease samples involving ferroptosis and pyroptosis. In the present study, ferroptosis and pyroptosis showed an imbalance in different keratinocyte lineages of psoriatic skinin addition to a unique pyroptosis-sensitive keratinocyte subset in atopic dermatitis (AD) skin. The results also revealed that pyroptosis and ferroptosis are involved in epidermal melanocyte destruction in vitiligo. Aberrant ferroptosis has been detected in multiple sclerosis, systemic sclerosis-associated interstitial lung disease, Crohn’s disease, and autoimmune orchitis. Cell line models adopted in the study also identified pro-inflammatory factors that can drive changes in ferroptosis and pyroptosis. Conclusion These results provide a unique perspective on the involvement of ferroptosis and pyroptosis in the pathological process of autoimmune diseases at the scRNA-seq level. IFN-γ is a critical inducer of pyroptosis sensitivity, and has been identified in two cell line models.

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Section: Discussionsupporting

confidence: 93%

Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level

Zhang

et al. 2022

J Transl Med

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“…To sum up, ferroptosis mainly relies on iron metabolism, lipid metabolism, and antioxidant metabolism, resulting in a significant accumulation of lipid peroxides in tumor cells and thus inducing cell death [ 74 ]. Therefore, various strategies to induce ferroptosis have been applied to cancer treatment, including triggering Fenton reaction by accumulating iron ions, inhibiting GPX4 activity or reducing the expression of GSH, inhibiting System Xc- activity, and exogenous delivery of lipid peroxide.…”

Section: New Approaches To Metal Ions-induced Cell Death and Their An...mentioning

confidence: 99%

New anti-cancer explorations based on metal ions

et al. 2022

J Nanobiotechnol

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Due to the urgent demand for more anti-cancer methods, the new applications of metal ions in cancer have attracted increasing attention. Especially the three kinds of the new mode of cell death, including ferroptosis, calcicoptosis, and cuproptosis, are of great concern. Meanwhile, many metal ions have been found to induce cell death through different approaches, such as interfering with osmotic pressure, triggering biocatalysis, activating immune pathways, and generating the prooxidant effect. Therefore, varieties of new strategies based on the above approaches have been studied and applied for anti-cancer applications. Moreover, many contrast agents based on metal ions have gradually become the core components of the bioimaging technologies, such as MRI, CT, and fluorescence imaging, which exhibit guiding significance for cancer diagnosis. Besides, the new nano-theranostic platforms based on metal ions have experimentally shown efficient response to endogenous and exogenous stimuli, which realizes simultaneous cancer therapy and diagnosis through a more controlled nano-system. However, most metal-based agents have still been in the early stages, and controlled clinical trials are necessary to confirm or not the current expectations. This article will focus on these new explorations based on metal ions, hoping to provide some theoretical support for more anti-cancer ideas.

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“…Ferroptosis suppression has been shown to increase tumorigenesis, and ferroptosis plays a vital role in malignancy development [ 14 ]. The mechanistic explanation of ferroptosis in melanoma growth, however, is still unknown [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

lncRNA AGAP2-AS1 Facilitates Tumorigenesis and Ferroptosis Resistance through SLC7A11 by IGF2BP2 Pathway in Melanoma

Huang

et al. 2022

Computational and Mathematical Methods in Medicine

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Long noncoding RNAs (lncRNAs) stand as indispensable regulators of initiation and development in melanoma (melanoma). However, the action molecular mechanisms linked to melanoma remain unclear. In the current study, the findings revealed that AGAP2-AS1 was considerably greater in melanoma than in healthy tissues and that the level of AGAP2-AS1 in cancer tissue was significantly linked to the cancerous TNM stage of patients. Individuals with high AGAP2-AS1 had a considerably shorter survival duration than patients with low AGAP2-AS1, regardless of progression-free survival or overall survival. Functionally, downregulating the expression of AGAP2-AS1 can inhibit the growth of melanocytes. Compared with the control group, AGAP2-AS1 knockdown increased Erastin-mediated iron death in melanoma cells. However, iron death inhibitor FERSINT-1 restored this effect, while Erastin induced melanoma cell death. Besides, intracellular iron and Fe2+ levels increased after AGAP2-AS1 knockdown in melanoma cells treated with Erastin compared with the si-NC group. In addition, AGAP2-AS1 silencing resulted in a significant decrease in glutathione (GSH) content in Erastin-treated melanoma cells. The mechanistic results suggest AGAP2-AS1 increases SLC7A11 mRNA stability through the IGF2BP2 pathway. In this investigation, we discovered new activities for AGAP2-AS1 and firstly discovered its mechanistic basis in ferroptosis and melanoma formation that might help in the search for potential therapy options in melanoma.

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Altered expression of ferroptosis markers and iron metabolism reveals a potential role of ferroptosis in vitiligo

Cited by 19 publications

References 36 publications

Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level

Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level

New anti-cancer explorations based on metal ions

lncRNA AGAP2-AS1 Facilitates Tumorigenesis and Ferroptosis Resistance through SLC7A11 by IGF2BP2 Pathway in Melanoma

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