CXCL14 Accelerates Fibroblast Ferroptosis in Inflammatory Bowel Disease by Regulating Lipid Metabolism via SCD1 DOI Creative Commons

Zhihua HE,

Lan Lin,

Chen Nini

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 18, 2023

Abstract Inflammatory bowel disease (IBD), historically subdivided into Crohn’s and ulcerative colitis, is a chronic, relapsing heterogeneous condition, resulting in intestinal tissue destruction dysfunction, such as fibrosis. Currently, there no effective therapy against colon Fibroblasts are known to contribute the pathogenesis of IBD-related Recently, our laboratory found that inflammatory fibroblasts IBD had significantly upregulated Chemokine (C-X-C motif) ligand 14 (CXCL14) expression, suggesting potential role CXCL14 Employing Dextran sodium sulfate(DSS)-induced chronic we showed was specifically collagen-secreting fibrotic mouse colons. In addition, human fibroblast (HIF CCD18) culture supernatants induced by transforming growth factor-β1 (TGF-β1), whereas overexpression sufficient promote ferroptosis. Mechanistically, CXCL14, transcriptionally decreasing transcript abundance stearoyl-CoA desaturase-1 (SCD1), mediated its pro-ferroptosis effects enforcing ERK signaling activity inhibiting p70 KDa ribosomal protein S6 kinase (S6K) activation fibroblasts. Using S100 calcium binding A4 (S100a4)-cre mice, generated an fibroblast-specific knockout line through Adeno-associated virus vectors (AAV) injection tail veins. We demonstrated deletion accelerated progression established fibrosis dextran sulfate (DSS)-induced therapeutic targeting for IBD.

Language: Английский

ADAM17/PTGS2 Facilitates Pulmonary Fibrosis by Regulating Ferroptosis DOI Creative Commons

Suyan Yan,

Yaqi Zhao, Wei Xu

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(5)

Published: March 1, 2025

ABSTRACT Pulmonary fibrosis (PF) is a chronic and progressive interstitial lung disease characterised by excessive deposition of extracellular matrix (ECM), resulting in high mortality rates. In this study, we provide evidence that ADAM17/PTGS2 plays crucial role inducing ferroptosis fibroblasts, promoting PF. Initially, an assessment was made ADAM17 protein levels patients diagnosed with connective tissue diseases–interstitial diseases (CTD‐ILD), using ELISA assays. Confirmation the relationship between achieved stimulating cells PMA or TAPI‐1 (the inhibitor), conjunction fibrosis‐inducing factor, TGFβ1. To further explore major downstream proteins contributing to altered PF, employed mRNA transcriptomics. investigate fibrosis, western blot assays, immunofluorescence transmission electron microscopy (TEM). Furthermore, effects ADAM17/PTGS2/ferroptosis pathway PF were verified Adeno‐associated virus (AAV)‐mediated gene knockdown mice. CTD‐ILD patients, expression significantly elevated. Upon stimulation, fibroblasts exhibited increased fibrosis‐related proteins, combined stimulation TGFβ1 synergistically promoted cellular fibrosis. Conversely, alleviated fibrotic induced Transcriptomic analysis fibroblast specimens overexpressing revealed elevated PTGS2 levels. Knockdown inhibition assays demonstrated regulates via PTGS2, ultimately deficiency bleomycin‐induced inflammation These findings first novel mechanism for regulating PF; it provides new theoretical basis exploring treatment

Language: Английский

Citations

0
Targeting PIM1 by Bruceine D attenuates skin fibrosis via myofibroblast ferroptosis DOI Creative Commons

Jianzhang Wang,

Yajuan Song,

Xiao-Ying Tan

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: unknown, P. 103619 - 103619

Published: March 1, 2025

Language: Английский

Citations

0
The Role of JPX in Regulating FUS/SLC7A11 Signaling Pathway Mediated Ferroptosis in Keloid Fibroblasts and its Potential in Scar Repair DOI

Jiyao Tang,

Zhaoming Huang, Panpan Yu

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: unknown, P. 151770 - 151770

Published: April 1, 2025

Language: Английский

Citations

0
Targeting ferroptosis with natural products in liver injury: new insights from molecular mechanisms to targeted therapies DOI Open Access
Yongyi Liang,

Shaojun Qiu,

Youwen Zou

et al.

Phytomedicine, Journal Year: 2023, Volume and Issue: 122, P. 155134 - 155134

Published: Oct. 4, 2023

Language: Английский

Citations

10
Analysis of the genetic characteristics and variations in disease-resistant grass carp based on whole-genome resequencing and transcriptome sequencing DOI Creative Commons

Huifang Tan,

Yude Wang, Biao Hu

et al.

Reproduction and Breeding, Journal Year: 2024, Volume and Issue: 4(1), P. 22 - 31

Published: Jan. 5, 2024

Disease-resistant grass carp (DR-GGC) was obtained by backcrossing gynogenetic (GGC, 2n = 48, female) with common (Ctenopharyngodon idellus [GC], male). The genetic constitution and the potential mutation associated growth dominance in DR-GGC were analyzed genomic situ hybridization (GISH), whole-genome resequencing (WGRS) RNA-sequencing (RNA-seq). GISH results showed partial translocations deletions chromosomes of compared GC. WGRS demonstrated that there numerous variations between its parents, among which had highest heterozygosity GGC purity. RNA-seq revealed differentially expressed genes (DEGs) significantly enriched cellular processes immune pathways Meanwhile, combined analysis identified DEGs overlapping loci These growth, metabolism, immunity, including biosynthesis, glycolysis/gluconeogenesis, extra matrix (ECM) receptor interactions. provide a basis for exploring better characteristics disease resistance than GC, valuable information on breeding carp, further understanding individuals.

Language: Английский

Citations

3
Protective effects of sulfated polysaccharides from Enteromorpha intestinalis on oxidative stress, liver iron overload and Ferroptosis in Zebra fish exposed to ethanol DOI Open Access

Marziyeh Khazaei,

Rashid Alijani Ardeshir

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 181, P. 117715 - 117715

Published: Nov. 29, 2024

Language: Английский

Citations

3
IFN-γ could induce ferroptosis in keloid fibroblasts by inhibiting the expression of serpine2 DOI Creative Commons
Jingyan Huang, Shun Yu,

Jing Luo

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: May 5, 2025

Abstract Keloids are common pathological scars resulting from previous trauma or inflammation. Interferon-gamma (IFN-γ) has shown significant therapeutic effects when used alone in combination with other agents. While IFN-γ been found to regulate ferroptosis tumor cells, its ability keloid fibroblasts (KFs) is unclear. Here, we have demonstrated a direct causal relationship between levels and KFs. To explore the intrinsic mechanism, performed genome-wide RNA proteomics sequencing that serpine2 was most significantly downregulated gene KFs after exogenous overexpression of IFN-γ. Serpine2, which belongs family serine protease inhibitors, play an important role fibrotic diseases. Therefore, hypothesized downstream regulation by Our results showed promotes collagen synthesis, turn proliferation, migration, invasive functions We further promoted system Xc − transporter expression, cystine uptake, glutathione enhanced GPX4 activity; inhibited reactive oxygen species generation. This resulted reduction intracellular lipid peroxidation metabolite malondialdehyde, as well reversed these overexpression. These were largely confirmed vivo models too. findings imply not only directly induces but also enhances their sensitivity inhibiting synthesis SLC7A11 SLC3A2 through downregulation serpine2. In summary, suggest serpine2-system axis promising target for treatment keloids.

Language: Английский

Citations

0
Is retrograde menstruation a universal, recurrent, physiological phenomenon? A systematic review of the evidence in humans and non-human primates DOI Creative Commons
Paola Viganò, Francesca Caprara, Francesca Giola

et al.

Human Reproduction Open, Journal Year: 2024, Volume and Issue: 2024(3)

Published: Jan. 1, 2024

What are the quantitative, qualitative, and temporal patterns of retrograde mentruation?

Language: Английский

Citations

2
Exploratory Analysis of Image-Guided Ionizing Radiation Delivery to Induce Long-Term Iron Accumulation and Ferritin Expression in a Lung Injury Model: Preliminary Results DOI Creative Commons
Amira Zaher, Bryce Duchman, Marina Ivanovic

et al.

Bioengineering, Journal Year: 2024, Volume and Issue: 11(2), P. 182 - 182

Published: Feb. 14, 2024

Background: Radiation therapy (RT) is an integral and commonly used therapeutic modality for primary lung cancer. However, radiation-induced injury (RILI) limits the irradiation dose in a significant source of morbidity. Disruptions iron metabolism have been linked to radiation injury, but underlying mechanisms remain unclear. Purpose: To utilize targeted delivery approach induce RILI development model system study role accumulation RILI. Methods: This utilizes Small Animal Research Platform (SARRP) target right with 20 Gy while minimizing delivered left adjacent heart. Long-term pulmonary function was performed using RespiRate-x64image analysis. Normal-appearing volumes were calculated cone beam CT (CBCT) image thresholding 3D Slicer software. Quantification spectrophotometrically ferrozine-based assay as well histologically Prussian blue via Western blotting ferritin heavy chain expression. Results: Mild fibrosis seen irradiated hematoxylin eosin-stained fixed tissue at 9 months, scoring from CBCT images, Szapiel system, highest fibrotic area metric. In contrast, no changes breathing rate observed, median survival not achieved up 36 weeks following irradiation, consistent mild when only one targeted. Our provided preliminary evidence on increased content expression lung, thus warranting further investigation. Conclusions: A may be useful studying long-term pathological effects associated ionizing radiation.

Language: Английский

Citations

1
Mechanistic insights into intrauterine adhesions DOI
Guangfeng Zhao, Yali Hu

Seminars in Immunopathology, Journal Year: 2024, Volume and Issue: 47(1)

Published: Nov. 29, 2024

Language: Английский

Citations

1