损伤神经元释放乳酸脱氢酶A促进中枢神经系统血管生成
文献 Extracellular Lactate Dehydrogenase A Release From Damaged Neurons Drives Central Nervous System Angiogenesis 于 2017年 发表在 EBioMedicine 原文链接
Abstract：
Angiogenesis, a prominent feature of pathology, is known to be guided by factors secreted by living cells around a lesion. Although many cells are disrupted in a response to injury, the relevance of degenerating cells in pathological angiogenesis is unclear. Here, we show that the release of lactate dehydrogenase A (LDHA) from degenerating neurons drives central nervous system (CNS) angiogenesis. Silencing neuronal LDHA expression suppressed angiogenesis around experimental autoimmune encephalomyelitis (EAE)- and controlled cortical impact-induced lesions. Extracellular LDHA-mediated angiogenesis was dependent on surface vimentin expression and vascular endothelial growth factor receptor (VEGFR) phosphorylation in vascular endothelial cells. Silencing vimentin expression in vascular endothelial cells prevented angiogenesis around EAE lesions and improved survival in a mouse model of glioblastoma. These results elucidate novel mechanisms that may mediate pathologic angiogenesis and identify a potential molecular target for the treatment of CNS diseases involving angiogenesis.
摘要：
血管生成作为病理学的显著特征，由病变周围活细胞分泌的因子诱导。尽管许多细胞在损伤反应中被破坏，但退化细胞与病理性血管生成的联系尚不清楚。本研究证明退化的神经元释放乳酸脱氢酶A(LDHA)促进中枢神经系统(CNS)的血管生成。从而抑制神经元LDHA的表达，抑制实验性自身免疫性脑脊髓炎(EAE)周围血管生成，并控制皮层冲击损伤。胞外LDHA介导的血管生成依赖于血管内皮细胞表面波形蛋白的表达和血管内皮生长因子受体(VEGFR)的磷酸化。通过抑制血管内皮细胞波形蛋白的表达，抑制EAE病变周围血管生成，提高胶质母细胞瘤小鼠模型的存活率。这些结果阐明了介导病理性血管生成的新机制，并为血管生成相关的CNS疾病治疗提供了一个潜在的分子靶点。
使用试剂原文信息：
The 8000×g-non-precipitable and 100,000×g-precipitable cell lysate fractions were incubated with His-tagged recombinant LDHA (USCN) or a 6 × His-tag peptide (Abcam) for 2 h at 4℃.
Mice were subcutaneously injected with 200 μl BD Matrigel Matrix Growth Factor Reduced (BD Biosciences) containing 10 μg/ml mouse recombinant LDHA (USCN).
The primary antibodies used were as follows: mouse α-tubulin (1:1000, sc-5286; Santa Cruz Biotechnology, RRID:AB_628411), rabbit anti-LDHA (1:1000, PAB370Mu01; USCN),
The primary antibodies were as follows: chicken anti-vimentin (1:250, AB5733; Millipore, RRID:AB_11212377) and rabbit anti-LDHA (1:100, PAB370Mu01, USCN).