Ritzenthaler Jeffrey D, Torres-Gonzalez Edilson, Janssen-Heininger Yvonne, Watson Walter H, Roman Jesse
Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
The Jane and Leonard Korman Respiratory Institute, Thomas Jefferson University, 834 Walnut Street, Suite 650, Philadelphia, PA, 19107, USA.
Lung. 2025 May 26;203(1):64. doi: 10.1007/s00408-025-00818-2.
Oxidative stress has been implicated in lung injury and repair. We seek to understand how alterations in the plasma redox potential (Eh) of the thiol disulfide couple cysteine (Cys) and cystine (CySS) (Eh Cys/CySS) affect this process. Previously, we reported that Eh Cys/CySS oxidation promotes a pro-fibrotic phenotype in lung fibroblasts and identified the cystine/glutamate exchanger solute carrier family 7, member 11 (Slc7a11) as a regulator of Eh Cys/CySS. We also observed that pharmacological agents capable of altering Slc7a11 expression affect lung fibroblast phenotype in vitro. We hypothesized that alterations in Slc7a11 expression would affect lung injury in vivo and set out to test this in C57Bl6 mice exposed to bleomycin. However, we did not observe changes in bleomycin-induced lung injury in animals treated with pharmacological alterations in Slc7a11 expression or when Slc7a11 knockout animals were tested. Thus, the role of Slc7a11 in lung injury remains uncertain.
氧化应激与肺损伤和修复有关。我们试图了解硫醇二硫化物对（半胱氨酸（Cys）和胱氨酸（CySS））的血浆氧化还原电位（Eh）（Eh Cys/CySS）的改变如何影响这一过程。此前，我们报道Eh Cys/CySS氧化促进肺成纤维细胞中的促纤维化表型，并确定胱氨酸/谷氨酸交换体溶质载体家族7成员11（Slc7a11）为Eh Cys/CySS的调节因子。我们还观察到，能够改变Slc7a11表达的药物制剂在体外会影响肺成纤维细胞表型。我们假设Slc7a11表达的改变会影响体内肺损伤，并着手在暴露于博来霉素的C57Bl6小鼠中进行测试。然而，在用Slc7a11表达的药理学改变处理的动物中，或在测试Slc7a11基因敲除动物时，我们未观察到博来霉素诱导的肺损伤有变化。因此，Slc7a11在肺损伤中的作用仍不确定。
