Department of Basic Medical Sciences, Neurosciences and Sensory Organs, Section of Human Anatomy and Histology, University of Bari Medical School Bari, University of Bari, Italy.
Brain Res Bull. 2019 Apr;147:69-77. doi: 10.1016/j.brainresbull.2019.01.023. Epub 2019 Jan 31.
A fraction of patients affected by Duchenne Muscular Dystrophy (DMD) shows mental disability as a consequence of neuronal and metabolic alteration. In this study, we evaluated the effect of α-methyl-prednisolone (PDN) on the expression of the angiogenic marker HIF1α, VEGFA and VEGFR-2 (FLK1) in correlation with PKC expression in the brain of mdx mouse, an experimental model of DMD. We demonstrated that HIF1α, VEGFA and FLK1 are overexpressed in the brain of dystrophic mdx mice in parallel with an increase of PKC expression and reduction of the tight junctions Occludin leading to altered angiogenesis. Moreover, we demonstrated that PDN treatment induces a significant reduction in the HIF1α, VEGF, FLK1, and PKC mRNA and proteins levels and restores Occludin expression reducing its phosphorylation pattern. Our results suggest a new mechanism of action of PDN that through PKC suppression normalizes the angiogenesis in dystrophic mdx brains.
一小部分患有杜氏肌营养不良症（DMD）的患者会出现神经和代谢改变导致的精神残疾。在这项研究中，我们评估了α-甲基强的松龙（PDN）对 mdx 小鼠脑内血管生成标志物 HIF1α、VEGFA 和 VEGFR-2（FLK1）表达的影响，并与 PKC 表达相关。我们证明 HIF1α、VEGFA 和 FLK1 在 DMD 模型 mdx 小鼠的大脑中过度表达，同时 PKC 表达增加，紧密连接 Occludin 减少，导致血管生成改变。此外，我们还证明 PDN 治疗可显著降低 HIF1α、VEGF、FLK1 和 PKC mRNA 和蛋白水平，并恢复 Occludin 的表达，减少其磷酸化模式。我们的研究结果表明 PDN 的一种新作用机制，即通过抑制 PKC 使 DMD 模型小鼠的血管生成恢复正常。
