研究表明VEGF可以提高牛视网膜内皮细胞和周细胞CTGF mRNA的表达,呈时间依赖性和剂量依赖性,提出CTGF在视网膜新生血管疾病中有重要作用,可能参与血管形成和组织纤维化[10]。He等[12]
分析研究了13例手术剥离AMD的CNV,并研究了CTGF对脉络膜内皮细胞(CEC)的作用。发现CNV膜上存在强烈的CTGF蛋白的表达,免疫双标记显示CTGF在RPE和CEC细胞上共同表达。可以显著诱导CECs的粘附和移行,但不刺激CECs增生。转化生长因子TGF-β和VEGF均可以上调CECs中CTGF蛋白的表达。而Watanabe等[3]同样的研究发现CTGF、TGF-β在CNV膜血管内皮细胞、RPE细胞及间质细胞(成纤维细胞样细胞、多角形血管周细胞)中强烈表达,并且纤维成分占主要的CNV 膜中的CTGF阳性信号强于细胞成分占主要的CNV膜,而TGF-β的表达相反。结果表明TGF-β上调CTGF表达,CTGF在脉络膜新生血管形成的病理
发展过程中有重要作用。我们发现,光镜下CNV膜由色素性巨噬细胞、迁移增殖的RPE细胞、和长梭形的成纤维细胞样细胞组成,CTGFmRNA一部分阳性标记位于CNV及附近梭形组织,另一部分阳性标记位于血管内皮细胞及神经节细胞层。这类细胞是否分泌CTGF或有CTGF的受体存在,还需要进一步的实验证实。在激光诱导的CNV膜中,CTGFmRNA在光凝后1wk有阳性表达,光凝后3,4wk,随着CNV膜的发展,CTGFmRNA阳性表达增强。这可能是因为 CNV膜形成是个创伤愈合过程,它包括3个阶段:炎症、增生、重塑。在CNV膜形成初期,细胞多纤维少,处于炎症、增生阶段,这一阶段TGF-β被上调,而CTGF未被上调 ,间质细胞只有微弱的CTGF表达。随着CTGF被上调,来源于间质细胞的CTGF刺激胞外基质的产生,刺激纤维形成。随后血管周细胞发生纤维变性促进CNV膜的发展纤维化[3]。这可能是CNV膜后期退化的原因。
尽管激光诱导的CNV模型和人新生血管的发生机制不同,但我们的研究证实CNV膜中有CTGFmRNA的表达,提示CTGF参与了CNV膜的形成和发展,但CTGF在CNV膜中的作用方式和基因调控机制还需要进一步的研究。
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