Tang Jianhui, Huang Zhaoming, Yu Panpan
Department of Medical Cosmetology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, Hubei, 437000, People's Republic of China.
Department of Medical Cosmetology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, Hubei, 437000, People's Republic of China.
Biochem Biophys Res Commun. 2025 May 12;763:151770. doi: 10.1016/j.bbrc.2025.151770. Epub 2025 Apr 9.
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.
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.
JPX regulates ferroptosis within fibroblast derived from scar tissue via the FUS/SLC7A11 pathway, demonstrating its potential utility in facilitating scar repair processes.
瘢痕疙瘩是一种由成纤维细胞异常增殖引发的纤维化疾病，受铁死亡影响。本研究旨在阐明长链非编码RNA JPX调控瘢痕疙瘩成纤维细胞铁死亡的机制。
我们从接受瘢痕疙瘩治疗的患者身上获取了30份瘢痕疙瘩组织样本和相邻的正常皮肤组织样本，随后从瘢痕疙瘩病变部位和未受影响部位分离出成纤维细胞。使用qRT-PCR检测这些病变和成纤维细胞样本中JPX的表达水平。然后，我们通过RNA免疫沉淀和放线菌素D实验验证了JPX对FUS和SLC7A11的调控作用。随后，我们在有或没有铁死亡抑制剂Fer-1的条件下，在瘢痕疙瘩成纤维细胞中过表达或沉默JPX和/或SLC7A11，通过MTT、Transwell和蛋白质免疫印迹实验评估细胞活力、迁移、侵袭、细胞外基质（ECM）标志物，并评估细胞铁含量、活性氧（ROS）、丙二醛（MDA）和谷胱甘肽（GSH）水平以及铁死亡相关蛋白的表达，以评估铁死亡情况。JPX在瘢痕疙瘩组织和瘢痕疙瘩成纤维细胞中上调。JPX通过FUS促进SLC7A11的稳定性和表达。JPX沉默抑制了瘢痕疙瘩成纤维细胞的活力、迁移、侵袭和ECM产生，但促进了其铁死亡，而Fer-1或SLC7A11过表达可逆转这些作用。
JPX通过FUS/SLC7A11途径调节瘢痕组织来源的成纤维细胞中的铁死亡，显示出其在促进瘢痕修复过程中的潜在作用。
