The Role of JPX in Regulating FUS/SLC7A11 Signaling Pathway Mediated Ferroptosis in Keloid Fibroblasts and its Potential in Scar Repair
Brief intro:
- Author: Jianhui Tang, Zhaoming Huang, Panpan Yu
- Journal: Biochemical and Biophysical Research Communications
- Doi: https://www.doi.org/10.1016/j.bbrc.2025.151770
- Publication Date: 2025 Apr 9
Abstract
Background: Keloid scar, a fibrotic disease initiated by aberrant fibroblast proliferation, is influenced by ferroptosis. This investigation aims to elucidate the mechanism of lncRNA JPX regulating ferroptosis in keloid fibroblasts.
Methods and results: We procured 30 samples of keloid tissue and adjacent normal skin tissues from patients undergoing treatment for keloid scars, subsequently isolating fibroblasts from both the keloid lesions and unaffected portions. JPX expression levels in these lesion and keloid fibroblast samples were detected using qRT-PCR. We then validated the regulatory role of JPX on FUS and SLC7A11 through RNA immunoprecipitation and actinomycin D assays. Subsequently, we overexpressed or silenced JPX and/or SLC7A11 in keloid fibroblasts under conditions with or without ferroptosis inhibitor Fer-1, assessing cell viability, migration, invasion, extracellular matrix (ECM) markers via MTT, Transwell and Western blot assays, and evaluating cellular iron content, reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) levels as well as the expression of ferroptosis-related proteins to assess ferroptosis. JPX was up-regulated in keloid tissue and keloid fibroblasts. JPX promoted SLC7A11 stability and expression through FUS. JPX silence suppressed viability, migration, invasion and ECM production, yet facilitated ferroptosis of keloid fibroblasts, while these effects could be reversed by Fer-1 or SLC7A11 overexpression.
Conclusion: JPX regulates ferroptosis within fibroblast derived from scar tissue via the FUS/SLC7A11 pathway, demonstrating its potential utility in facilitating scar repair processes."
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