Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Institute of Translational and Precision Medicine, Nantong University, Nantong 226001, China.
Biosci Rep. 2020 Apr 30;40(4). doi: 10.1042/BSR20200287.
In the light of hepatocyte growth factor (HGF) the inhibiting role on the expression of hepcidin, we hypothesized that HGF might be able to reduce cell and tissue iron by increasing ferroportin 1 (Fpn1) content and Fpn1-mediated iron release from cells and tissues. The hypothesized ability of HGF to reduce iron might be one of the mechanisms associated with its neuroprotective action under the conditions of ischemia/reperfusion (I/R). Here, we investigated the effects of HGF on the expression of hepcidin as well as transferrin receptor 1 (TfR1), divalent metal transporter 1 (DMT1), Fpn1, ferritin and iron regulatory proteins (IRPs) in oxygen-glucose deprivation and reoxygenation (OGD/R)-treated PC12 cells by real-time PCR and Western blot analysis. We demonstrated that HGF could completely reverse the OGD/R-induced reduction in Fpn1 and IRP1 expression and increase in ferritin light chain protein and hepcidin mRNA levels in PC12 cells. It was concluded that HGF protects PC12 cells against OGD/R-induced injury mainly by reducing cell iron contents via the up-regulation of Fpn1 and increased Fpn1-mediated iron export from cells. Our findings suggested that HGF may also be able to ameliorate OGD/R or I/R-induced overloading of brain iron by promoting Fpn1 expression.
鉴于肝细胞生长因子（HGF）对铁调素表达的抑制作用，我们假设 HGF 可能通过增加亚铁转运蛋白 1（Fpn1）的含量和 Fpn1 介导的细胞和组织中铁的释放来减少细胞和组织中的铁。HGF 减少铁的能力可能是其在缺血/再灌注（I/R）条件下发挥神经保护作用的相关机制之一。在这里，我们通过实时 PCR 和 Western blot 分析研究了 HGF 对氧葡萄糖剥夺和复氧（OGD/R）处理的 PC12 细胞中铁调素以及转铁蛋白受体 1（TfR1）、二价金属转运蛋白 1（DMT1）、Fpn1、铁蛋白和铁调节蛋白（IRPs）表达的影响。结果表明，HGF 可完全逆转 OGD/R 诱导的 Fpn1 和 IRP1 表达减少以及铁蛋白轻链蛋白和铁调素 mRNA 水平升高。结论是 HGF 通过上调 Fpn1 和增加 Fpn1 介导的铁从细胞中的输出，保护 PC12 细胞免受 OGD/R 诱导的损伤，主要是通过降低细胞内铁含量。我们的研究结果表明，HGF 还可能通过促进 Fpn1 表达来改善 OGD/R 或 I/R 引起的脑铁过载。
