5-ALA-PDT induced ferroptosis in keloid fibroblasts via ROS, accompanied by downregulation of xCT, GPX4

Zhang, Jiheng; Liu, Lulu; Li, Xinying; Shen, Xiaoxiao; Yang, Guanlin; Deng, Yumeng; Hu, Z. W.; Zhang, Junbo; Lu, Yuangang

doi:10.1016/j.pdpdt.2023.103612

Cited by 12 publications

(4 citation statements)

References 69 publications

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“…A bioinformatics analysis has identified several novel ferroptosis-related diagnostic markers in keloid, indicating that ferroptosis is associated with the development of keloid ( Zeng et al, 2024 ). Moreover, 5-aminolevulinic acid–based photodynamic therapy (5-ALA-PDT) exerted cytotoxic activity by increasing ROS and inducing ferroptosis in KFs ( Zhang et al, 2023 ). Notably, iron overload is one of the characteristics of ferroptosis.…”

Section: Discussionmentioning

confidence: 99%

Ferrostatin-1 inhibits fibroblast fibrosis in keloid by inhibiting ferroptosis

Yang,

Li,

Wang

2024

PeerJ

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Background Keloid is a chronic proliferative fibrotic disease caused by abnormal fibroblasts proliferation and excessive extracellular matrix (ECM) production. Numerous fibrotic disorders are significantly influenced by ferroptosis, and targeting ferroptosis can effectively mitigate fibrosis development. This study aimed to investigate the role and mechanism of ferroptosis in keloid development. Methods Keloid tissues from keloid patients and normal skin tissues from healthy controls were collected. Iron content, lipid peroxidation (LPO) level, and the mRNA and protein expression of ferroptosis-related genes including solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), transferrin receptor (TFRC), and nuclear factor erythroid 2-related factor 2 (Nrf2) were determined. Mitochondrial morphology was observed using transmission electron microscopy (TEM). Keloid fibroblasts (KFs) were isolated from keloid tissues, and treated with ferroptosis inhibitor ferrostatin-1 (fer-1) or ferroptosis activator erastin. Iron content, ferroptosis-related marker levels, LPO level, mitochondrial membrane potential, ATP content, and mitochondrial morphology in KFs were detected. Furthermore, the protein levels of α-smooth muscle actin (α-SMA), collagen I, and collagen III were measured to investigate whether ferroptosis affect fibrosis in KFs. Results We found that iron content and LPO level were substantially elevated in keloid tissues and KFs. SLC7A11, GPX4, and Nrf2 were downregulated and TFRC was upregulated in keloid tissues and KFs. Mitochondria in keloid tissues and KFs exhibited ferroptosis-related pathology. Fer-1 treatment reduced iron content, restrained ferroptosis and mitochondrial dysfunction in KFs, Moreover, ferrostatin-1 restrained the protein expression of α-SMA, collagen I, and collagen III in KFs. Whereas erastin treatment showed the opposite results. Conclusion Ferroptosis exists in keloid. Ferrostatin-1 restrained ECM deposition and fibrosis in keloid through inhibiting ferroptosis, and erastin induced ECM deposition and fibrosis through intensifying ferroptosis.

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Section: Discussionmentioning

confidence: 99%

Ferrostatin-1 inhibits fibroblast fibrosis in keloid by inhibiting ferroptosis

Yang,

Li,

Wang

2024

PeerJ

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“…As reported, ferroptosis induction in keloid fibroblasts was able to attenuate keloids. [ 159 ] Furthermore, ACSL4 inhibition was found to prevent inflammatory macrophage ferroptosis and alleviate skin fibrosis in systemic sclerosis. [ 160 ] Despite limited evidence, ferroptosis is undeniably one of the important mechanisms leading to skin fibrosis.…”

Section: Ferroptosis and Other Fibrotic Organsmentioning

confidence: 99%

Ferroptosis in organ fibrosis: From mechanisms to therapeutic medicines

Lai,

Wang,

Huang

et al. 2024

Journal of Translational Internal Medicine

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Fibrosis occurs in many organs, and its sustained progress can lead to organ destruction and malfunction. Although numerous studies on organ fibrosis have been carried out, its underlying mechanism is largely unknown, and no ideal treatment is currently available. Ferroptosis is an iron-dependent process of programmed cell death that is characterized by lipid peroxidation. In the past decade, a growing body of evidence demonstrated the association between ferroptosis and fibrotic diseases, while targeting ferroptosis may serve as a potential therapeutic strategy. This review highlights recent advances in the crosstalk between ferroptosis and organ fibrosis, and discusses ferroptosis-targeted therapeutic approaches against fibrosis that are currently being explored.

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“…Subsequently, Zheng demonstrated for the first time that 5-ALA-PDT can induce tumor cell pyroptosis . In 2023, Lu observed 5-ALA-PDT-induced ferroptosis in tumor cells . It may be due to the unclear targets of available photosensitizers, leaving the intrinsic mechanisms and specific pathways of inducing tumor cell death accidental.…”

Section: Introductionmentioning

confidence: 99%

Two-Photon Photodegradation of E3 Ubiquitin Ligase Cereblon by a Ru(II) Complex: Inducing Ferroptosis in Cisplatin-Resistant Tumor Cells

Lin,

Zheng,

Xiong

et al. 2024

J. Med. Chem.

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Using photodynamic therapy (PDT) to trigger nonconventional cell death pathways has provided a new scheme for highly efficient and non-side effects to drug-resistant cancer therapies. Nonetheless, the unclear targets of available photosensitizers leave the manner of PDT-induced tumor cell death relatively unpredictable. Herein, we developed a novel Ru(II)-based photosensitizer, Ru-Poma. Possessing the E3 ubiquitin ligase CRBN-targeting moiety and high singlet oxygen yield of 0.96, Ru-Poma was demonstrated to specifically photodegrade endogenous CRBN, increase lipid peroxide, downregulate GPX4 and GAPDH expression, and consequently induce ferroptosis in cisplatin-resistant cancerous cells. Furthermore, with the deep penetration of two-photon excitation, Ru-Poma achieved drug-resistant circumvention in a 3D tumor cell model. Thus, we describe the first sample of the CRBN-targeting Ru(II) complex active in PDT.

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5-ALA-PDT induced ferroptosis in keloid fibroblasts via ROS, accompanied by downregulation of xCT, GPX4

Cited by 12 publications

References 69 publications

Ferrostatin-1 inhibits fibroblast fibrosis in keloid by inhibiting ferroptosis

Ferrostatin-1 inhibits fibroblast fibrosis in keloid by inhibiting ferroptosis

Ferroptosis in organ fibrosis: From mechanisms to therapeutic medicines

Two-Photon Photodegradation of E3 Ubiquitin Ligase Cereblon by a Ru(II) Complex: Inducing Ferroptosis in Cisplatin-Resistant Tumor Cells

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