Spliet Wim G M, Aronica Eleonora, Ramkema Marja, Aten Jan, Troost Dirk
Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Acta Neuropathol. 2003 Nov;106(5):449-57. doi: 10.1007/s00401-003-0741-y. Epub 2003 Aug 12.
Connective tissue growth factor (CTGF) is a secreted protein involved in a variety of cellular events such as survival, proliferation, and extracellular matrix production. Recent studies suggest a role for this protein also in the repair processes of the central nervous system. The distribution and significance of CTGF in human brain is, however, poorly understood, particularly under pathological conditions. In the present study the expression of CTGF protein was investigated in the spinal cord of control and both sporadic and familial amyotrophic lateral sclerosis (sALS and fALS) patients. Western blot analysis showed a consistent increase in CTGF expression in six sALS patients compared with controls. Immunoreactivity signal for CTGF was equally present in blood vessels of control and ALS spinal cord, but was dramatically increased in reactive astrocytes of the ventral horn and white matter in both sALS and fALS. Increased expression was also observed in the cytoplasm of motor neurons of sALS and fALS patients with long duration of the disease. Our data indicate a role for CTGF in the complex reactive process that is associated with the progression of ALS spinal cord damage. The up-regulation in reactive astrocytes supports a role for CTGF in the molecular mechanisms underlying astrogliosis. However, the altered CTGF expression observed in neurons might represent an additional mechanism involved in motor neuron dysfunction and changes in glial-neuronal communication in the course of the neurodegenerative process.
结缔组织生长因子（CTGF）是一种分泌蛋白，参与多种细胞活动，如存活、增殖和细胞外基质生成。最近的研究表明，这种蛋白在中枢神经系统的修复过程中也发挥作用。然而，人们对CTGF在人脑中的分布和意义了解甚少，尤其是在病理条件下。在本研究中，我们调查了CTGF蛋白在对照脊髓以及散发性和家族性肌萎缩侧索硬化症（sALS和fALS）患者脊髓中的表达情况。蛋白质印迹分析显示，与对照相比，6例sALS患者的CTGF表达持续增加。CTGF的免疫反应信号在对照和ALS脊髓的血管中均有出现，但在sALS和fALS患者的腹角和白质的反应性星形胶质细胞中显著增加。在病程较长的sALS和fALS患者的运动神经元细胞质中也观察到表达增加。我们的数据表明，CTGF在与ALS脊髓损伤进展相关的复杂反应过程中发挥作用。反应性星形胶质细胞中的上调支持了CTGF在星形胶质细胞增生潜在分子机制中的作用。然而，在神经元中观察到的CTGF表达改变可能代表了神经退行性过程中运动神经元功能障碍以及胶质-神经元通讯变化所涉及的另一种机制。
