Rah Bilal, Shafarin Jasmin, Qaisar Rizwan, Karim Asima, Hamad Mawieh, Muhammad Jibran Sualeh
Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, , United Arab Emirates.
Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, , United Arab Emirates; Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
Life Sci Space Res (Amst). 2025 May;45:7-15. doi: 10.1016/j.lssr.2025.01.003. Epub 2025 Jan 18.
Microgravity exposure can impact various physiological systems, yet its specific effects on liver cells remain inadequately studied. To address this gap, we used a hindlimb unloading (HU) mouse model to simulate microgravity conditions and investigate alterations in iron metabolism within liver and skeletal muscle cells. 16-week-old male C57BL/6j mice were divided into three groups: (i) ground-based control (GC), (ii) hindlimb unloading treated with vehicle (HU-v), and (iii) hindlimb unloading treated with deferoxamine (DFO). After three weeks, mice were euthanized, and samples of gastrocnemius muscle, liver, and serum were collected for analysis. The HU-v group exhibited significant muscle and liver cell atrophy compared to the GC group, along with disrupted iron metabolism, as indicated by altered expression of key iron regulatory proteins, including FTH1, FPN, TFR1, IRP-1, HMOX-1, and Hepcidin. In contrast, the DFO group demonstrated restored iron homeostasis, with protein expression patterns resembling those of the GC group. Serum analysis revealed elevated levels of serum iron, ferritin, and transferrin in the DFO group compared to both HU-v and GC groups, albeit with minimal changes in total iron-binding capacity. These findings suggest that simulated microgravity induces iron overload and cellular atrophy in liver and skeletal muscle cells, highlighting the potential therapeutic benefits of iron chelation in such conditions.
微重力暴露会影响各种生理系统，但其对肝细胞的具体影响仍研究不足。为填补这一空白，我们使用后肢卸载（HU）小鼠模型来模拟微重力条件，并研究肝脏和骨骼肌细胞中铁代谢的变化。16周龄雄性C57BL/6j小鼠被分为三组：（i）地面对照组（GC），（ii）用赋形剂处理的后肢卸载组（HU-v），以及（iii）用去铁胺（DFO）处理的后肢卸载组。三周后，对小鼠实施安乐死，并采集腓肠肌、肝脏和血清样本进行分析。与GC组相比，HU-v组出现明显的肌肉和肝细胞萎缩，同时铁代谢紊乱，关键铁调节蛋白（包括FTH1、FPN、TFR1、IRP-1、HMOX-1和铁调素）的表达发生改变。相比之下，DFO组铁稳态得以恢复，蛋白表达模式与GC组相似。血清分析显示，与HU-v组和GC组相比，DFO组血清铁、铁蛋白和转铁蛋白水平升高，尽管总铁结合能力变化极小。这些发现表明，模拟微重力会导致肝脏和骨骼肌细胞中铁过载和细胞萎缩，凸显了在此类情况下铁螯合的潜在治疗益处。
