Angiopoietin-like 7 secretion is induced by glaucoma stimuli and its concentration is elevated in glaucomatous aqueous humor
Angiopoietin-like 7 secretion is induced by glaucoma stimuli and its concentration is elevated in glaucomatous aqueous humor
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DOI：
10.1167/iovs.07-1347
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发表时间：
2008-08-01
影响因子：
4.4
通讯作者：
Kuchtey, Rachel W.
中科院分区：
文献类型：
--
作者：
Kuchtey, John;Kallberg, Maria E.;Kuchtey, Rachel W.
目的.探讨血管生成素样7（ANGPTL 7）蛋白参与青光眼发病机制的可能性。方法。用地塞米松（DEX）或转化生长因子β（TGF β）刺激原代人小梁网（TM）细胞和角巩膜外植体，并通过Western印迹分析测定分泌到培养基中的ANGPTL7蛋白。通过免疫细胞化学研究ANGPTL7在转染的永生化TM细胞系中稳定过表达对胶原表达的影响。通过免疫组织化学方法确定ANGPTL7蛋白在人眼中的定位。通过Western印迹分析比较青光眼患者和对照患者的房水（AH）中ANGPTL7蛋白的浓度。原发性开角型青光眼（POAG）的比格犬模型用于将犬AH中ANGPTL7蛋白水平与疾病进展相关联。TGF β和DEX刺激TM细胞和角巩膜外植体分泌ANGPTL7蛋白。通过永生化TM细胞系过表达ANGPTL7增加I型胶原的表达。ANGPTL7蛋白的表达位于角膜基质中，靠近利姆布斯，并且遍及巩膜，在TM中表达较低。在筛板中，ANGPTL7表达与筛板相关。ANGPTL7蛋白的浓度在青光眼患者的AH中升高，并且在POAG比格犬中随着疾病的进展而增加。青光眼刺激诱导ANGPTL7分泌和青光眼AH中ANGPTL7浓度增加表明ANGPTL7在青光眼中过表达。由于ANGPTL7的过表达增加了胶原蛋白的表达，这是一种潜在的疾病机制，因此ANGPTL7可能在青光眼中具有致病作用，并可作为潜在的治疗靶点。
PURPOSE. To investigate the possibility that Angiopoietin-like 7 (ANGPTL7) protein is involved in the pathogenesis of glaucoma.METHODS. Primary human trabecular meshwork (TM) cells and corneoscleral explants were stimulated with either dexamethasone (DEX) or transforming growth factor beta (TGF beta), and ANGPTL7 protein secreted into culture medium was determined by Western blot analysis. The effect of stable overexpression of ANGPTL7 in transfected immortalized TM cell lines on collagen expression was investigated by immunocytochemistry. Localization of ANGPTL7 protein in human eyes was determined by immunohistochemistry. The concentration of ANGPTL7 protein in aqueous humor (AH) from patients with glaucoma and control patients was compared by Western blot analysis. The beagle model of primary open-angle glaucoma (POAG) was used to correlate ANGPTL7 protein levels in canine AH with disease progression.RESULTS. TGF beta and DEX stimulated secretion of ANGPTL7 protein by TM cells and corneoscleral explants. Overexpression of ANGPTL7 by immortalized TM cell lines increased expression of type I collagen. Expression of ANGPTL7 protein was located in the corneal stroma, near the limbus, and throughout the sclera, with lower expression in the TM. In the lamina cribrosa, ANGPTL7 expression was associated with the cribriform plates. The concentration of ANGPTL7 protein was elevated in AH from patients with glaucoma and increased as disease progressed in POAG beagle dogs.CONCLUSIONS. Induction of ANGPTL7 secretion by glaucoma stimuli and increased concentration of ANGPTL7 in glaucomatous AH suggest that ANGPTL7 is overexpressed in glaucoma. Since overexpression of ANGPTL7 increases collagen expression, a potential disease mechanism, ANGPTL7 could have a pathogenic role in glaucoma, and may serve as a potential therapeutic target.